AMP vs. RPM

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Patrick Arnold said:
yeah they are basically non-steroidal anabolic steroids (yes thats an oxymoron)
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And because of that I kind of dislike the term P-SARM - the term sounds too "hype" and coined even when used to describe a superb product like RPM. Or does it..? :D

IMO, we should not be talking about SARMs - phytochemical or the real stuff - here in relation to RPM.

I'm not saying that RPM could not be classified as a P-SARM - in my mind, that is more of a matter of setting definitions and terminology than a measure of its potency.
 
xjsynx said:
Have you taken a Resveratrol product before?
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Sure. Did 1000 mg of Resveratrol along with 1000mg of Quercetin for a month just recently.

Just wonder where I did come up with an off-the-wall idea like that! ;)

Anyhow, Resveratrol is all over the newspapers nowadays for its anti-aging/rejuvenating effects, so I guess it's a trendy or even a sexy ingredient?
 
I bet PA likes sexy ingredients... :D

Maybe that's why he doesn't get all excited about RPM as it only lists "un-sexy" ingredients? ;)
 
Arzi75 said:
Sure. Did 1000 mg of Resveratrol along with 1000mg of Quercetin for a month just recently.

Just wonder where I did come up with an off-the-wall idea like that! ;)

Anyhow, Resveratrol is all over the newspapers nowadays for its anti-aging/rejuvenating effects, so I guess it's a trendy or even sexy ingredient?
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Ah recently. So, I guess you are jumping on the trend then?

I was taking Res in an Anti-E supplement a few years ago. I guess PA was too busy with the clear then???
 
rms80 said:
Wow:)

How would you market it?
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PS- Prohormones and Pro-steroids are not really an option with my company- I have no personal bias towards them- but I am aiming towards producing effective products that are compliant with the NCAA, NFL, IOC, and other governing sports bodies. Do not take this as a shot towards you or your company- I have been nothing but impressed with your products, and I really enjoyed your honesty during your interview with Bob Costas- we need more people out there fighting the good fight for this industry.

My background is in sports nutrition, biomechanics, and training theory, with a little bit of chem thrown in, but I don't have anything close to your knowledge base in that subject (unfortunately). A very wise person once told me to stick with what you know, and I am taking that same approach with my product formulations and company goals- I strive to make supplements that are extremely effective for sports performance, and yet allow you to pass a urinalysis from any governing body. Part of this equation is using my background in the aforementioned fields, and this weighs heavily into my formulations- I want to make athletes better, just like you, but I am taking a slightly different approach. From what I have seen- the main point we seem to differ on is whether or not I can make effective supplements from a list that you deem "nothing special"- I say yes, you say no- I guess we need to leave it up to the users of our respective products- yours are very effective, as well as mine- judging from all of the user feedback. From my POV, it is a LOT harder to make an effective supplement from a conglomeration of herbal extracts and non-"sexy" (I know, not very scientific) compounds- you do a good job at what you do, and I do a decent job at accomplishing this goal.

As far as the marketing- I give as much scientfic info as there is available on each compound, and then extrapolate from that point- P-SARM may be a stretch to you- but considering that I can't use steroidal components in my products- judging by the literature and the true definition of a SARM, it is not a stretch at all.


I train with a lot of elite guys (sprinters and hurdlers)- and I pay attention to EVERYTHING they tell me, athlete to athlete, and athlete to researcher- and I use this as a tool for formulating products as well- I don't have some of the resources you do- but I take what I have been given, and use it to my advantage- both to create better supplements, and to learn everything I can about this field.....
 
rms80 said:
PS- Prohormones and Pro-steroids are not really an option with my company- I have no personal bias towards them- but I am aiming towards producing effective products that are compliant with the NCAA, NFL, IOC, and other governing sports bodies. Do not take this as a shot towards you or your company- I have been nothing but impressed with your products, and I really enjoyed your honesty during your interview with Bob Costas- we need more people out there fighting the good fight for this industry.

My background is in sports nutrition, biomechanics, and training theory, with a little bit of chem thrown in, but I don't have anything close to your knowledge base in that subject (unfortunately). A very wise person once told me to stick with what you know, and I am taking that same approach with my product formulations and company goals- I strive to make supplements that are extremely effective for sports performance, and yet allow you to pass a urinalysis from any governing body. Part of this equation is using my background in the aforementioned fields, and this weighs heavily into my formulations- I want to make athletes better, just like you, but I am taking a slightly different approach. From what I have seen- the main point we seem to differ on is whether or not I can make effective supplements from a list that you deem "nothing special"- I say yes, you say no- I guess we need to leave it up to the users of our respective products- yours are very effective, as well as mine- judging from all of the user feedback. From my POV, it is a LOT harder to make an effective supplement from a conglomeration of herbal extracts and non-"sexy" (I know, not very scientific) compounds- you do a good job at what you do, and I do a decent job at accomplishing this goal.

As far as the marketing- I give as much scientfic info as there is available on each compound, and then extrapolate from that point- P-SARM may be a stretch to you- but considering that I can't use steroidal components in my products- judging by the literature and the true definition of a SARM, it is not a stretch at all.


I train with a lot of elite guys (sprinters and hurdlers)- and I pay attention to EVERYTHING they tell me, athlete to athlete, and athlete to researcher- and I use this as a tool for formulating products as well- I don't have some of the resources you do- but I take what I have been given, and use it to my advantage- both to create better supplements, and to learn everything I can about this field.....
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Excellent posting! :thumbsup:
 
xjsynx said:
Ah recently. So, I guess you are jumping on the trend then?
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Oops. I guess so then. Damn you caught me on this, bro! I bought the 6-OXO just because Resveratrol is trendy! ;)

I hope I did not buy RPM just because RPM is "trendy"? I hope not! ;)
 
Lanbane said:
The best thing to do would be to back up and add in that RPM is not merely a pre-workout product. It'll hang in there with the herbal anabolics on the market any day.
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So is RPM vs Leviathin a better comp or is Leviathin more like a thermo?
 
Arzi75 said:
Why would PA have put chocamine in with geranamine if it would negate its effects?

I have never heard chocamine blunting the effect of geranamine, but then again I'm no scientist, either.

So, maybe it was because of this that Patrick changed the chocamine in AMP?
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slow down

i did not change the chocamine in amp.. and i am just theorizing about chocamine interacting in the formula
 
Patrick Arnold said:
slow down

i did not change the chocamine in amp.. and i am just theorizing about chocamine interacting in the formula
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u gotta watch it. If you say "we were making some runs of AMP and some caps feel on the floor" ur gonna see "PA said each bottle of AMP is short some caps."
 
Arzi75 said:
I bet PA likes sexy ingredients... :D

Maybe that's why he doesn't get all excited about RPM as it only lists "un-sexy" ingredients? ;)
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did i lose you somewhere?

i am criticizing the use of misleading and pseudo-scientific marketing

the ingredients are fine
 
Patrick Arnold said:
i would market it honestly. i probably would not sell as many bottles right off the bat but i would be able to look at myself in the mirror every night with dignity
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I would say "this is a pre-workout performance enhancer/ energy product that also increases libido." When I see all that SARM stuff I stop reading. There is a MHP product with a fancy SARM writeup, Ive tried to read it 3x but cant force myself 2. Im looking around like, "where's the SARM (whatever that is), I see HGW."
 
rms80 said:
PS
As far as the marketing- I give as much scientfic info as there is available on each compound, and then extrapolate from that point- P-SARM may be a stretch to you- but considering that I can't use steroidal components in my products- judging by the literature and the true definition of a SARM, it is not a stretch at all.

.....
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you cannot use steroidal ingredients in your product EDIT: Enough.

A SARM is a selective androgen receptor modulator. So name the compound in your product that binds and activates the androgen receptor.

I have read the research on Icariin and it qualifies for this definition about as much as something like protodioscin
 
Arzi75 said:
What's the true definition of a SARM? ;)
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SARMs were basically developed as replacements for anabolic steroids.

The quest to differentiate between anabolic and androgenic effects by structural modifications to the steroid molecule went on for years but no one ever quite was able to get true selective anabolism

now that chemists have powerful computer generated molecular modeling tools they are able to conceive "virtual" molecules and predict their binding to the androgen receptor. These molecules have structures that don't resemble steroids at all, but because of their spatial and electrochemical properties they still can bind strongly

They then go to the labs and try to synthesize these molecules.

Usually they start with a basic scaffold structure and add on functional groups and carbon bonds etc.

that is what a SARM is - and it has nothing to do with a f*cking flavone derivative from horny goat weed
 
Chuck Diesel said:
I would say "this is a pre-workout performance enhancer/ energy product that also increases libido." When I see all that SARM stuff I stop reading. There is a MHP product with a fancy SARM writeup, Ive tried to read it 3x but cant force myself 2. Im looking around like, "where's the SARM (whatever that is), I see HGW."
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Chuck understands
 
Patrick Arnold said:
SARMs were basically developed as replacements for anabolic steroids.

The quest to differentiate between anabolic and androgenic effects by structural modifications to the steroid molecule went on for years but no one ever quite was able to get true selective anabolism

now that chemists have powerful computer generated molecular modeling tools they are able to conceive "virtual" molecules and predict their binding to the androgen receptor. These molecules have structures that don't resemble steroids at all, but because of their spatial and electrochemical properties they still can bind strongly

They then go to the labs and try to synthesize these molecules.

Usually they start with a basic scaffold structure and add on functional groups and carbon bonds etc.

that is what a SARM is - and it has nothing to do with a f*cking flavone derivative from horny goat weed
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I like AN and I like their products as I am currently running a log on their IGF-2 product. I used RPN and enjoyed it quite a bit, I just lament the P-Sarm use in the advertising.
 
Patrick Arnold said:
Chuck understands
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No offense, but Chuck also sees HGW in the MHP Sarm-X writeup.......

Anyways, all in all.... it seems we agree to disagree. I think a comparison between AMP and RPM is not really a valid comparison; as they are used for slightly different things, and are marketed towards slightly different individuals. A summary I am confident that the majority of the market will agree with is that both products are very good at what they do.
 
Lanbane said:
No offense, but Chuck also sees HGW in the MHP Sarm-X writeup.......

Anyways, all in all.... it seems we agree to disagree. I think a comparison between AMP and RPM is not really a valid comparison; as they are used for slightly different things, and are marketed towards slightly different individuals. A summary I am confident that the majority of the market will agree with is that both products are very good at what they do.
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I dont see HGW in the MHP Sarm-x writeup, I really dont know whats in the MHP product, when i saw all the Sarm talk I stop reading because I know MHP makes natural products so it was probably some mumbo jumbo bs. I was refering to when I was reading on RPM and I saw Sarm in the write-up, then I did a double take on the sup facts because I didnt think there was anything in there to be referred to with some new fancy language. But its along the lines of listing Caffeine as "Methyl Xanthine Anhydrous Caffeine" when thats the same thing as just saying Caffeine, or Caffeine Anhydrous. Since that group compounds are called Methy Xanthines, I guess its better to put that in front of caffeine because when consumers see Methyl.... they think its some super caffeine. Glad people like the product but you have to understand when companies use fancy names for common ingredients and these hi-tech write-ups its going to draw some criticisms.

I hate proprietary caffeine amounts in products. But anyway RPM sells and people seem to like it at varrying dosages.
 
Chuck Diesel said:
I dont see HGW in the MHP Sarm-x writeup, I really dont know whats in the MHP product, when i saw all the Sarm talk I stop reading because I know MHP makes natural products so it was probably some mumbo jumbo bs. I was refering to when I was reading on RPM and I saw Sarm in the write-up, then I did a double take on the sup facts because I didnt think there was anything in there to be referred to with some new fancy language. But its along the lines of listing Caffeine as "Methyl Xanthine Anhydrous Caffeine" when thats the same thing as just saying Caffeine, or Caffeine Anhydrous. Since that group compounds are called Methy Xanthines, I guess its better to put that in front of caffeine because when consumers see Methyl.... they think its some super caffeine. Glad people like the product but you have to understand when companies use fancy names for common ingredients and these hi-tech write-ups its going to draw some criticisms.

I hate proprietary caffeine amounts in products. But anyway RPM sells and people seem to like it at varrying dosages.
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:D

Understandable- I see your point of view and I see PA's- I stated my position on this and he stated his (a little more strongly). The bottom line is this: I stand by my claims and I stand by my product. We list the real ingredients in the product, and the product is effective. The scientific definition for a SARM has been clearly delineated- but the definition for a phytochemical (icariin) with SARM-like properties has not. I have numerous different studies that back up the claim that icariin fits many of the criteria for a SARM, all of them are referenced in the RPM write-up on our website. As far as being a "bastardization of science", I disagree with that as well. Hell, there is a first time for scientific classification for everything- look at Linnaeus- w/o him taking the time to classify different species, we wouldn't have the modern system of taxonomy.......


So please allow me to excuse myself from something I don't really give a **** about being involved in, and a thread that I did not even start- I am replying to this thread only because I am a little curious as to the point of this little discussion- I am not going to sit here and throw out insults or get into a pissing match about who is smarter- it is a waste of time that all of us could be using to do something productive- baking a cake, surfing internet porn, table tennis, deadlifting, luge lessons, or whatever it is you guys do for fun- while you guys do this- I will be out there doing what I do.....so please, by all means, enjoy yourselves ;)
 
Just to be fair in stating my point of view, here is some of the research I am basing my claims off of:

Asian J Androl. 2006 Sep;8(5):601-5. Epub 2006 Jun 5. Links
The testosterone mimetic properties of icariin.Zhang ZB, Yang QT.
Department of Urology, Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, China. [email protected]

AIM: To evaluate the testosterone mimetic properties of icariin. METHODS: Forty-eight healthy male Sprague-Dawley rats at the age of 15 months were randomly divided into four groups with 12 rats each: the control group ©, the model group (M), the icariin group (ICA) and the testosterone group (T). The reproductive system was damaged by cyclophosphamide (intraperitoneal injection, 20 mg/kg x day) for 5 consecutive days for groups M, ICA and T, at the sixth day, ICA (gastric gavage, 200 mg/kg x day) for the ICA group and sterandryl (subcutaneous injection, 5 mg/rat . day) for the T group for 7 consecutive days, respectively. The levels of serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), serum bone Gla-protein (BGP) and tartrate-resistant acid phosphatase activity in serum (StrACP) were determined. The histological changes of the testis and the penis were observed by microscope with hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase biotin-dUTP-X nick end labeling (TUNEL), respectively. RESULTS: (1) Icariin improved the condition of reproductive organs and increased the circulating levels of testosterone. (2) Icariin treatment also improved the steady-state serum BGP and might have promoted bone formation. At the same time, it decreased the serum levels of StrACP and might have reduced the bone resorption. (3) Icarrin suppressed the extent of apoptosis of penile cavernosal smooth muscle cells. CONCLUSION: Icariin has testosterone mimetic properties and has therapeutic potential in the management of hypoandrogenism.

J Huazhong Univ Sci Technolog Med Sci. 2005;25(6):690-2. Links
Effects of Icariin on expression of OPN mRNA and type I collagen in rat osteoblasts in vitro.Xiao Q, Chen A, Guo F.
Department of orthopaedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

To study the effects of Icariin on expression of osteopontin (OPN) mRNA and type I collagen in rat osteoblasts in vitro and to explore its possible mechanisms in preventing osteoporosis. OB was isolated from calvaria of new-born new-born fetal Sprague-Dawley (superdrol) rats by means of modified sequential collagenase digestion and incubated in MEM medium and the cell morphology was observed under inverted phase contrast microscope, OB was identified by alkaline phosphatase (ALP) staining. Different concentration (0.1 microg/mL, 1.0 microg/ml, 10 microg/mL) of Icariin was added to the OB and incubated. The effect of Icariin on the proliferation and osteogenesis of OB was monitored by MTT analysis. The expression of type I collagen was estimated with immunohistochemistry techniques. The expression levels of mRNA of OPN in the cells in every group were examined by reverse-transcriptase ploymerase chain reaction (RT-PCR). The expression of OPN mRNA and type I collagen was strengthened gradually with the increase of Icariin concentration and peaked with 10 microg/mL Icariin on the 5th day. Icariin could significantly promote the expression of OPN mRNA and type I collagen in rat osteoblasts in vitro. The levels of expression of OPN mRNA and type I collagen were changed with different concentration of Icariin. Icariin could effectively prevent and treat osteoporosis and promote the bone formation.

Pharmazie. 2005 Dec;60(12):939-42. Links
Icariin, a flavonoid from the herb Epimedium enhances the osteogenic differentiation of rat primary bone marrow stromal cells.Chen KM, Ge BF, Ma HP, Liu XY, Bai MH, Wang Y.
Institute of Orthopaedics, Lanzhou General Hospital, Lanzhou, Gansu 730050, PR China. [email protected]

The herb Epimedium has long been used in Traditional Chinese Medicine to treat bone fracture and prevent osteoporosis. Researchers believe that the flavonoids contained in the herb are the effective component for this activity. However, no single flavonoid has been studied for its effect on bone-related cells. In the present study, icariin, one of the major flavonoids of the herb, supplemented the primary culture medium of rat bone marrow stromal cells (rMSCs) at 0.1 microM , 1 microM and 10 microM respectively. It was found that icariin stimulated the proliferation of rMSCs and increased the number of CFU-F stained positive for alkaline phosphatase in a dose-dependent manner. Icariin also dose-dependently increased the alkaline phosphatase activity, osteoalcin secretion and calcium deposition level of rMSCs during osteogenic induction. The addition of 10 microM icariin caused four times more mineralized bone nodules to be formed by rMSCs than in the control. The results demonstrated that icariin should be an effective component for bone-strengthening activity, and one of the mechanisms is to stimulate the proliferation and enhance the osteogenic differentiation of MSCs.

Pharmacol Biochem Behav. 2005 Dec;82(4):686-94. Epub 2005 Dec 27. Links
Antidepressant-like effect of icariin and its possible mechanism in mice.Pan Y, Kong L, Xia X, Zhang W, Xia Z, Jiang F.
State Key Laboratory of Pharmaceutical Biotechnology, Immunobiological Laboratory, Institute of Functional Biomolecule, Nanjing University, PR China.

The behavioral, neurochemical and neuroendocrine effects of icariin isolated from Epimedium brevicornum were investigated in behavioral despair models of KunMing strain of male mice. Icariin was found to significantly shorten immobility time in the forced swimming test (FST) after orally administration for 21 consecutive days. Icarrin also produced a marked reduction in immobility time in the tail suspension test (TST) when administered for at least 7 consecutive days. The preferable antidepressant action by icariin was obtained at 17.5 and 35 mg/kg in the present study. Moreover, it was observed that the stress of FST exposure induced increases in brain monoamine oxidase (MAO) A and B activities, serum corticotropin-releasing factor (CRF) levels, as well as decreases in brain monoamine neurotransmitter levels. Treatment of icariin for 21 consecutive days mainly reversed the above effects in the mouse FST. These results suggested that icarrin possessed potent antidepressant-like properties that were mediated via neurochemical and neuroendocrine systems.

Asian J Androl. 2005 Dec;7(4):381-8. Links
Effects of icariin on erectile function and expression of nitric oxide synthase isoforms in castrated rats.Liu WJ, Xin ZC, Xin H, Yuan YM, Tian L, Guo YL.
Andrology Center of Peking University First Hospital, Beijing 100009, China.

AIM: To investigate the effect of icariin on erectile function and the expression of nitric oxide synthase (NOS) isoforms in castrated rats. METHODS: Thirty-two adult male Wistar rats were randomly divided into one sham-operated group (A) and three castrated groups (B, C and D). One week after surgery, rats were treated with normal saline (groups A and cool.gif or oral icariin (1 mg/[kg.day] for group C and 5 mg/[kg.day] for group D) for 4 weeks. One week after treatment, the erectile function of the rats was assessed by measuring intracavernosal pressure (ICP) during electrostimulation of the cavernosal nerve. The serum testosterone (ST) levels, the percent of smooth muscle (PSM) in trabecular tissue, and the expression of mRNA and proteins of neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS) and phosphodiesterase V (PDE5) in corpus cavernosum (CC) were also evaluated. RESULTS: ICP, PSM, ST and the expression of nNOS, iNOS, eNOS and PDE5 were significantly decreased in group B compared with those in group A (P 0.01). However, ICP, PSM and the expression of nNOS and iNOS were increased in groups C and D compared with those in group B (P 0.05). Changes in ST and the expression of eNOS and PDE5 were not significant (P 0.05) in groups C and D compared with those in group B. CONCLUSION: Oral treatment with icariin ( 98.6 % purity) for 4 weeks potentially improves erectile function. This effect is correlated with an increase in PSM and the expression of certain NOS in the CC of castrated rats. These results suggest that icariin may have a therapeutic effect on erectile dysfunction.

Wei Sheng Yan Jiu. 2005 Mar;34(2):191-3. Links
[Effects of Icariin on ovariectomized osteoporotic rats][Article in Chinese]
Bao JR, Yang JW, Li SF, Zhao W, Zhang Q, Yan Y.
Life Science College, Northeast Agricultural University, Harbin 150030, China.

OBJECTIVE: To observe the effects of Icariin on ovariectomized osteoporotic rats. METHODS: Female Wistar rats were ovariectomized and administered different dosage of Icariin and 17beta-estradiol for eight weeks. Bone mineral density (BMD), indexes of biomechanics and bone metabolism-associated biochemical markers were measured. RESULTS: Icariin increased the BMD, maximum load and flexural rigidity in the osteoporotic rats. The activities of serum tartrate-resistant acid phosphatase (TRACP) and bone alkaline phosphatase (BALP) were decreased in the Icraiin-fed ovariectomized rats. CONCLUSION: Icariin 225mg/kg per day could increase the BMD and improve indexes of bone biomechanics in ovariectomized osteoporotic rats. It was effective in preventing bone loss induced by ovariectomy.
 
And here are some SARM studies as a basis of comparison:

Selective Androgen Receptor Modulator (SARM) Treatment Improves Muscle Strength and Body Composition, and Prevents Bone Loss in Orchidectomized Rats
Wenqing Gao, Peter J. Reiser, Christopher C. Coss, Mitch A. Phelps, Jeffrey D. Kearbey, Duane D. Miller, and James T. Dalton*

Division of Pharmaceutics, College of Pharmacy, Department of Oral Biology, College of Dentistry, The Ohio State University, Columbus, OH 43210; Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis, TN 38163



The partial agonist activity of a selective androgen receptor modulator (SARM) in the prostate was demonstrated in our previous study (Endocrinology 145(12):5420-28, 2004). In the current study, we characterized the full agonist activity of S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide (a structurally related SARM referred to in other publications and hereafter as S-4) in skeletal muscle, bone and pituitary of castrated male rats. Twelve weeks after castration, animals were treated with S-4 (3 or 10 mg/kg), dihydrotestosterone (DHT) (3 mg/kg), or vehicle for 8 weeks. S-4 (3 and 10 mg/kg) restored soleus muscle mass and strength and levator ani muscle mass to that seen in intact animals. Similar changes were also observed in DHT (3 mg/kg) treated animals. Compared with the anabolic effects observed in muscle, DHT (3 mg/kg) stimulated prostate and seminal vesicle weights over 2-fold greater than that observed in intact controls, while S-4 (3 mg/kg) returned these androgenic organs to only 16% and 17%, respectively, of the control levels. S-4 (3, 10 mg/kg) and DHT (3 mg/kg) restored castration-induced loss in lean body mass. Furthermore, S-4 treatment caused a significantly larger increase in total body bone mineral density (BMD) than DHT. S-4 (3 and 10 mg/kg) also demonstrated agonist activity in the pituitary, and significantly decreased plasma LH and FSH levels in castrated animals in a dose dependent manner. In summary, the strong anabolic effects of S-4 in skeletal muscle, bone, and pituitary were achieved with minimal pharmacologic effect in the prostate. The tissue selective pharmacologic activity of SARMs provides obvious advantages over steroidal androgen therapy and demonstrates the promising therapeutic utility that this new class of drugs may hold.

A Selective Androgen Receptor Modulator (SARM) for Hormonal Male Contraception
Jiyun Chen 1, Dong Jin Hwang 2, Casey E. Bohl 1, Duane D. Miller 2, James T. Dalton 1*

1 Division of Pharmaceutics, College of Pharmacy, The Ohio State University 2 Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis

Abstract

The recent discovery of nonsteroidal selective androgen receptor modulators (SARMs) provides a promising alternative for testosterone replacement therapies, including hormonal male contraception. The identification of an orally bioavailable SARM with the ability to mimic the central and peripheral androgenic and anabolic effects of testosterone would represent an important step toward the "male pill". We characterized the in vitro and in vivo pharmacologic activity of (S)-3-(4-Chloro-3-fluorophenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethylphenyl)propionamide ( C-6), a novel SARM developed in our laboratories. C-6 was identified as an androgen receptor (AR) agonist with high AR binding affinity (Ki = 4.9 nM). C-6 showed tissue-selective pharmacologic activity with higher anabolic activity than androgenic activity in male rats. The dose required to maintain the weight of the prostate, seminal vesicles, and levator ani muscle to one-half of the size of the maximum effects (i.e., ED50) was 0.78 ± 0.06, 0.88 ± 0.1 and 0.17 ± 0.04 mg/day, respectively. As opposed to other SARMs, gonadotropin levels in C-6-treated groups were significantly lower than control values. C-6 also significantly decreased serum testosterone concentration in intact rats after two weeks treatment. Marked suppression of spermatogenesis was observed after 10 weeks treatment with C-6 in intact male rats. Pharmacokinetic studies of C-6 in male rats revealed that C-6 was well absorbed after oral administration (bioavailability 76%), with a long (6.3 h) half-life at a dose of 10 mg/kg. These studies show that C-6 mimicked the in vivo pharmacologic and endocrine effects of testosterone while maintaining the oral bioavailability and tissue-selective actions of nonsteroidal SARMs.

Curr Opin Investig Drugs. 2006 Oct;7(10):873-81.Links
Selective androgen receptor modulators: in pursuit of tissue-selective androgens.
Omwancha J, Brown TR.

Johns Hopkins Bloomberg School of Public Health, Department of Biochemistry and Molecular Biology, Division of Reproductive Biology, 615 North Wolfe Street, Baltimore, MD 21205, USA.

The androgen receptor mediates the androgenic and anabolic activity of the endogenous steroids testosterone and 5alpha-dihydrotestosterone. Current knowledge of the androgen receptor protein structure, and the molecular mechanisms surrounding the binding properties and activities of agonists and antagonists has led to the design and development of novel nonsteroidal ligands with selected tissue-specific androgen receptor agonist and antagonist activities. The activity of these compounds, termed selective androgen receptor modulators (SARMs), is directed toward the maintenance or enhancement of anabolic effects on bone and muscle with minimal androgenic effects on prostate growth. SARMs are of potential therapeutic value in the treatment of male hypogonadism, osteoporosis, frailty and muscle wasting, burn injury and would healing, anemia, mood and depression, benign prostatic hyperplasia and prostate cancer.

J Musculoskelet Neuronal Interact. 2002 Mar;2(3):222-4.Links
Novel, non-steroidal, selective androgen receptor modulators (SARMs) with anabolic activity in bone and muscle and improved safety profile.
Rosen J, Negro-Vilar A.

Ligand Pharmaceuticals, San Diego, CA 92121, USA.

A novel approach to the treatment of osteoporosis in men, and possibly women, is the development of selective androgen receptor modulators (SARMs) that can stimulate formation of new bone with substantially diminished proliferative activity in the prostate, as well as reduced virilizing activity in women. Over the last several years, we have developed a program to discover and develop novel, non-steroidal, orally-active selective androgen receptor modulators (SARMs) that provide improved therapeutic benefits and reduce risk and side effects. In recent studies, we have used a skeletally mature orchiectomized (ORX) male rat as an animal model of male hypogonadism for assessing the efficacy of LGD2226, a nonsteroidal, non-aromatizable, and non-5alpha-reducible SARM. We assessed the activity of LGD2226 on bone turnover, bone mass and bone strength, and also evaluated the effects exerted on classic androgen-dependent targets, such as prostate, seminal vesicles and muscle. A substantial loss of bone density was observed in ORX animals, and this loss was prevented by SARMs, as well as standard androgens. Biochemical markers of bone turnover revealed an early increase of bone resorption in androgen-deficient rats that was repressed in ORX animals treated with the oral SARM, LGD2226, during a 4-month treatment period. Differences in architectural properties and bone strength were detected by histomorphometric and mechanical analyses, demonstrating beneficial effects of LGD2226 on bone quality in androgen-deficient rats. Histomorphometric analysis of cortical bone revealed distinct anabolic activity of LGD2226 in periosteal bone. LGD2226 was able to prevent bone loss and maintain bone quality in ORX rats by stimulating bone formation, while also inhibiting bone turnover. LGD2226 also exerted anabolic activity on the levator ani muscle. Taken together, these results suggest that orally-active, non-steroidal SARMs may be useful therapeutics for both muscle and bone in elderly hypogonadal men through their anabolic activities. Since SARMs both prevent bone loss, and also stimulate formation of new bone, they may have significant advantages relative to currently used anti-resorptive therapies. Coupled with their activity in muscle and their ability to maintain or restore libido, they offer new therapeutic approaches for male and female hormone replacement.
 
Lanbane said:
:clap2:
Click to expand...

I looked over the research some more this morning- and PA raised a couple of valid points- Icariin resembles a SERM as far as receptor binding- yet delivers effects that closely resemble those of a SARM- take a look:

A novel anticancer agent, icaritin, induced cell growth inhibition, G1 arrest and mitochondrial transmembrane potential drop in human prostate carcinoma PC-3 cells.




Icariin and icaritin with prenyl group have been demonstrated for their selective estrogen receptor modulating activities. We screened their effects on cell growth in human prostate carcinoma PC-3 cell line (estrogen receptor positive) in vitro. PC-3 cell line was used for the measurement of anti-carcinoma activities of 0-100 micromol/l icaritin and 30 micromol/l icariin. 1 micromol/l 17-beta estradiol (E(2)) served as the estrogen positive control, and 1 micromol/l ICI 182,780 [7 alpha-[9 (4,4,5,5,5-pentafluoropentyl) sulfinyl] nonyl]-estra-1,3,5(10)-triene-3,17h-diol]] served as the specific estrogen receptor antagonist. Primary cultured rat prostate basal cells used as cell growth selective control. The growth-inhibitory effects were analyzed using MTT assay, and fluorochrome staining, flow cytometry, and immunoblotting were employed to illustrate the possible mechanisms. When treated with icaritin for 24 to 72 h, cell growth was strongly inhibited (at 48 h IC(50) was 10.74+/-1.59 micromol/l, P<0.001) companied with a mitochondrial transmembrane potential (_Psim) drop. Meanwhile, few changes in IC(50) could be observed when co-incubated with ICI 182,780. Icaritin-induced growth inhibition was associated with G(1) arrest (P<0.05), and G(2)-M arrest depending upon doses. Consistently with G(1) arrest, icaritin increased protein expressions of pRb, p27(Kip1) and p16(Ink4a), while showed decrease in phosphorylated pRb, Cyclin D1 and CDK4. Comparatively, icariin has much lower effects on PC-3 cells and showed only weak G(1) arrest, suggesting a possible structure-activity relationship. These findings suggested a novel anticancer efficacy of icaritin mediated selectively via induction of cell cycle arrest but not associated with estrogen receptors in PC-3 cells.


Yet icariin (unlike a lot of other epimedium-based metabolites) exhibits no actual estrogenic activity:

Taxonomic, genetic, chemical and estrogenic characteristics of Epimedium species.

A


To understand the factors contributing to estrogenic properties of extracts from the genus Epimedium L. (Berberidaceae), we performed taxonomic, genetic and chemical characterization on 37 specimens from 18 species and related these to estrogen receptor (ERalpha and ERbeta) bioactivity, as measured by reporter genes in stable human cells. Boot strap values derived from amplified fragment length polymorphisms indicated that specimens of E. koreanum, E. brevicornum, E. myrianthum, E. leishanense, and E. membranaceum were genetically distinct and this was supported by their very similar ERalpha activities. In contrast, specimens from E. pubescens and E. sagittatum were diverse both genetically, chemically and in terms of ERalpha and ERbeta bioactivities. Strikingly, a genetic cluster comprising six rare Epimedium species exhibited strongest ERalpha and ERbeta activity, and this bioactivity was positively correlated with content of trace flavonoid aglycones (kaempferol, apigenin, quercetin, luteolin and breviflavone B). In contrast, there was no association between estrogenic activity and the major flavonol glycoside constituents (icariin and epimedin A-C). Although they exhibited equally strong ERalpha and ERbeta activity, E. koreanum can be clearly differentiated from E. pubescens and E. brevicornum by genetic distance and its significantly lower content of epimedin C. Our morphologic, genetic, chemical and bioactivity profiling provide the basis for the production of extracts with reproducible estrogenic properties. Such reproducibility will be critical for the standardization of Epimedium-based products.


Icariin has been shown to increase sexual drive and erectile function, both anecdotally and through research, and to also have testosterone mimetic effects, while not increasing estrogen.

Here is a study on men with Toremifene, another SERM:

The beneficial effects of toremifene administration on the hypothalamic-pituitary-testicular axis and sperm parameters in men with idiopathic oligozoospermia.

OBJECTIVE: To evaluate whether toremifene, a selective estrogen receptor modulator (SERM), has a beneficiary effect on all three main sperm parameters. DESIGN: Prospective interventional clinical study. SETTING: University hospital. PATIENT(S): One-hundred subfertile men with idiopathic oligozospermia. INTERVENTION(S): Toremifene (60 mg daily) was administered to all men for 3 months. At baseline and at the end of each month, serum concentrations of follicle-stimulating hormone (FSH), testosterone, inhibin B, and sex hormone-binding globulin (SHBG) were measured. At baseline and at the end, semen analysis was performed and sperm concentration, spermatozoal motility and normal sperm forms were determined. MAIN OUTCOME MEASURE(S): Gonadotropin, testosterone, inhibin-B levels, total sperm count, sperm morphology and motility. RESULT(S): Toremifene administration resulted in a significant increase in FSH, testosterone, SHBG, and inhibin B levels, as well as in sperm concentration, percentage motility and normal sperm forms. Twenty-two men's partners achieved pregnancy within 2 months of the end of treatment. At the end of the third month, serum FSH levels were significantly higher in the men whose partners did not achieve pregnancy, and total sperm count and normal sperm forms were significantly lower compared with the group of men whose partners achieved pregnancy. CONCLUSION(S): Toremifene administration for a period of 3 months in men with idiopathic oligozoospermia is associated with significant improvements of sperm count, motility, and morphology, mediated by increased gonadotropin secretion and possibly a direct beneficial effect of toremifene on the testes. The above findings are also indicative of a better testicular exocrine (improved sperm parameters) response to treatment in men whose partners achieved pregnancy compared with those who did not. Further randomized, placebo-controlled trials should be conducted to determine whether this particular selective estrogen receptor modulator can be useful as an initial approach in men with oligozoospermia.

SERMs and SARMs seem to have a lot of overlapping effects, especially in men- and icariin has effects that closely resemble both classes of compounds- icariin acts more like a conventional SERM with some characteristics, but more like a SARM with others.....
 
Lanbane said:
No offense, but Chuck also sees HGW in the MHP Sarm-X writeup.......

Anyways, all in all.... it seems we agree to disagree. I think a comparison between AMP and RPM is not really a valid comparison; as they are used for slightly different things, and are marketed towards slightly different individuals. A summary I am confident that the majority of the market will agree with is that both products are very good at what they do.
Click to expand...


what does HGW stand for?
 
rms80 said:
:D

Understandable- I see your point of view and I see PA's- I stated my position on this and he stated his (a little more strongly). The bottom line is this: I stand by my claims and I stand by my product. We list the real ingredients in the product, and the product is effective. The scientific definition for a SARM has been clearly delineated- but the definition for a phytochemical (icariin) with SARM-like properties has not. I have numerous different studies that back up the claim that icariin fits many of the criteria for a SARM, all of them are referenced in the RPM write-up on our website.
Click to expand...



according to your definition things like tribulus and tongkat ali also fit the definition.

It is simply deceitful for you to associate your product with SARMs, which are very sophisticated and powerful pharmaceutical products

i wish you would rethink your marketing approach. it may help you make some quick money but it will rapidly make you a pariah in this industry as well
 
rms80 said:
Just to be fair in stating my point of view, here is some of the research I am basing my claims off of:

Asian J Androl. 2006 Sep;8(5):601-5. Epub 2006 Jun 5. Links
The testosterone mimetic properties of icariin.Zhang ZB, Yang QT.
Department of Urology, Second Affiliated Hospital, Shantou University Medical College, Shantou 515041, China. [email protected]

AIM: To evaluate the testosterone mimetic properties of icariin. METHODS: Forty-eight healthy male Sprague-Dawley rats at the age of 15 months were randomly divided into four groups with 12 rats each: the control group ©, the model group (M), the icariin group (ICA) and the testosterone group (T). The reproductive system was damaged by cyclophosphamide (intraperitoneal injection, 20 mg/kg x day) for 5 consecutive days for groups M, ICA and T, at the sixth day, ICA (gastric gavage, 200 mg/kg x day) for the ICA group and sterandryl (subcutaneous injection, 5 mg/rat . day) for the T group for 7 consecutive days, respectively. The levels of serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), serum bone Gla-protein (BGP) and tartrate-resistant acid phosphatase activity in serum (StrACP) were determined. The histological changes of the testis and the penis were observed by microscope with hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase biotin-dUTP-X nick end labeling (TUNEL), respectively. RESULTS: (1) Icariin improved the condition of reproductive organs and increased the circulating levels of testosterone. (2) Icariin treatment also improved the steady-state serum BGP and might have promoted bone formation. At the same time, it decreased the serum levels of StrACP and might have reduced the bone resorption. (3) Icarrin suppressed the extent of apoptosis of penile cavernosal smooth muscle cells. CONCLUSION: Icariin has testosterone mimetic properties and has therapeutic potential in the management of hypoandrogenism.

J Huazhong Univ Sci Technolog Med Sci. 2005;25(6):690-2. Links
Effects of Icariin on expression of OPN mRNA and type I collagen in rat osteoblasts in vitro.Xiao Q, Chen A, Guo F.
Department of orthopaedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

To study the effects of Icariin on expression of osteopontin (OPN) mRNA and type I collagen in rat osteoblasts in vitro and to explore its possible mechanisms in preventing osteoporosis. OB was isolated from calvaria of new-born new-born fetal Sprague-Dawley (superdrol) rats by means of modified sequential collagenase digestion and incubated in MEM medium and the cell morphology was observed under inverted phase contrast microscope, OB was identified by alkaline phosphatase (ALP) staining. Different concentration (0.1 microg/mL, 1.0 microg/ml, 10 microg/mL) of Icariin was added to the OB and incubated. The effect of Icariin on the proliferation and osteogenesis of OB was monitored by MTT analysis. The expression of type I collagen was estimated with immunohistochemistry techniques. The expression levels of mRNA of OPN in the cells in every group were examined by reverse-transcriptase ploymerase chain reaction (RT-PCR). The expression of OPN mRNA and type I collagen was strengthened gradually with the increase of Icariin concentration and peaked with 10 microg/mL Icariin on the 5th day. Icariin could significantly promote the expression of OPN mRNA and type I collagen in rat osteoblasts in vitro. The levels of expression of OPN mRNA and type I collagen were changed with different concentration of Icariin. Icariin could effectively prevent and treat osteoporosis and promote the bone formation.

Pharmazie. 2005 Dec;60(12):939-42. Links
Icariin, a flavonoid from the herb Epimedium enhances the osteogenic differentiation of rat primary bone marrow stromal cells.Chen KM, Ge BF, Ma HP, Liu XY, Bai MH, Wang Y.
Institute of Orthopaedics, Lanzhou General Hospital, Lanzhou, Gansu 730050, PR China. [email protected]

The herb Epimedium has long been used in Traditional Chinese Medicine to treat bone fracture and prevent osteoporosis. Researchers believe that the flavonoids contained in the herb are the effective component for this activity. However, no single flavonoid has been studied for its effect on bone-related cells. In the present study, icariin, one of the major flavonoids of the herb, supplemented the primary culture medium of rat bone marrow stromal cells (rMSCs) at 0.1 microM , 1 microM and 10 microM respectively. It was found that icariin stimulated the proliferation of rMSCs and increased the number of CFU-F stained positive for alkaline phosphatase in a dose-dependent manner. Icariin also dose-dependently increased the alkaline phosphatase activity, osteoalcin secretion and calcium deposition level of rMSCs during osteogenic induction. The addition of 10 microM icariin caused four times more mineralized bone nodules to be formed by rMSCs than in the control. The results demonstrated that icariin should be an effective component for bone-strengthening activity, and one of the mechanisms is to stimulate the proliferation and enhance the osteogenic differentiation of MSCs.

Pharmacol Biochem Behav. 2005 Dec;82(4):686-94. Epub 2005 Dec 27. Links
Antidepressant-like effect of icariin and its possible mechanism in mice.Pan Y, Kong L, Xia X, Zhang W, Xia Z, Jiang F.
State Key Laboratory of Pharmaceutical Biotechnology, Immunobiological Laboratory, Institute of Functional Biomolecule, Nanjing University, PR China.

The behavioral, neurochemical and neuroendocrine effects of icariin isolated from Epimedium brevicornum were investigated in behavioral despair models of KunMing strain of male mice. Icariin was found to significantly shorten immobility time in the forced swimming test (FST) after orally administration for 21 consecutive days. Icarrin also produced a marked reduction in immobility time in the tail suspension test (TST) when administered for at least 7 consecutive days. The preferable antidepressant action by icariin was obtained at 17.5 and 35 mg/kg in the present study. Moreover, it was observed that the stress of FST exposure induced increases in brain monoamine oxidase (MAO) A and B activities, serum corticotropin-releasing factor (CRF) levels, as well as decreases in brain monoamine neurotransmitter levels. Treatment of icariin for 21 consecutive days mainly reversed the above effects in the mouse FST. These results suggested that icarrin possessed potent antidepressant-like properties that were mediated via neurochemical and neuroendocrine systems.

Asian J Androl. 2005 Dec;7(4):381-8. Links
Effects of icariin on erectile function and expression of nitric oxide synthase isoforms in castrated rats.Liu WJ, Xin ZC, Xin H, Yuan YM, Tian L, Guo YL.
Andrology Center of Peking University First Hospital, Beijing 100009, China.

AIM: To investigate the effect of icariin on erectile function and the expression of nitric oxide synthase (NOS) isoforms in castrated rats. METHODS: Thirty-two adult male Wistar rats were randomly divided into one sham-operated group (A) and three castrated groups (B, C and D). One week after surgery, rats were treated with normal saline (groups A and cool.gif or oral icariin (1 mg/[kg.day] for group C and 5 mg/[kg.day] for group D) for 4 weeks. One week after treatment, the erectile function of the rats was assessed by measuring intracavernosal pressure (ICP) during electrostimulation of the cavernosal nerve. The serum testosterone (ST) levels, the percent of smooth muscle (PSM) in trabecular tissue, and the expression of mRNA and proteins of neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS) and phosphodiesterase V (PDE5) in corpus cavernosum (CC) were also evaluated. RESULTS: ICP, PSM, ST and the expression of nNOS, iNOS, eNOS and PDE5 were significantly decreased in group B compared with those in group A (P 0.01). However, ICP, PSM and the expression of nNOS and iNOS were increased in groups C and D compared with those in group B (P 0.05). Changes in ST and the expression of eNOS and PDE5 were not significant (P 0.05) in groups C and D compared with those in group B. CONCLUSION: Oral treatment with icariin ( 98.6 % purity) for 4 weeks potentially improves erectile function. This effect is correlated with an increase in PSM and the expression of certain NOS in the CC of castrated rats. These results suggest that icariin may have a therapeutic effect on erectile dysfunction.

Wei Sheng Yan Jiu. 2005 Mar;34(2):191-3. Links
[Effects of Icariin on ovariectomized osteoporotic rats][Article in Chinese]
Bao JR, Yang JW, Li SF, Zhao W, Zhang Q, Yan Y.
Life Science College, Northeast Agricultural University, Harbin 150030, China.

OBJECTIVE: To observe the effects of Icariin on ovariectomized osteoporotic rats. METHODS: Female Wistar rats were ovariectomized and administered different dosage of Icariin and 17beta-estradiol for eight weeks. Bone mineral density (BMD), indexes of biomechanics and bone metabolism-associated biochemical markers were measured. RESULTS: Icariin increased the BMD, maximum load and flexural rigidity in the osteoporotic rats. The activities of serum tartrate-resistant acid phosphatase (TRACP) and bone alkaline phosphatase (BALP) were decreased in the Icraiin-fed ovariectomized rats. CONCLUSION: Icariin 225mg/kg per day could increase the BMD and improve indexes of bone biomechanics in ovariectomized osteoporotic rats. It was effective in preventing bone loss induced by ovariectomy.
Click to expand...

yes i have been aware of these studies for quite some time. these studies however provide zero support for the claim of being a SARM
 
rms80 said:
And here are some SARM studies as a basis of comparison:

Selective Androgen Receptor Modulator (SARM) Treatment Improves Muscle Strength and Body Composition, and Prevents Bone Loss in Orchidectomized Rats
Wenqing Gao, Peter J. Reiser, Christopher C. Coss, Mitch A. Phelps, Jeffrey D. Kearbey, Duane D. Miller, and James T. Dalton*

Division of Pharmaceutics, College of Pharmacy, Department of Oral Biology, College of Dentistry, The Ohio State University, Columbus, OH 43210; Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis, TN 38163



The partial agonist activity of a selective androgen receptor modulator (SARM) in the prostate was demonstrated in our previous study (Endocrinology 145(12):5420-28, 2004). In the current study, we characterized the full agonist activity of S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide (a structurally related SARM referred to in other publications and hereafter as S-4) in skeletal muscle, bone and pituitary of castrated male rats. Twelve weeks after castration, animals were treated with S-4 (3 or 10 mg/kg), dihydrotestosterone (DHT) (3 mg/kg), or vehicle for 8 weeks. S-4 (3 and 10 mg/kg) restored soleus muscle mass and strength and levator ani muscle mass to that seen in intact animals. Similar changes were also observed in DHT (3 mg/kg) treated animals. Compared with the anabolic effects observed in muscle, DHT (3 mg/kg) stimulated prostate and seminal vesicle weights over 2-fold greater than that observed in intact controls, while S-4 (3 mg/kg) returned these androgenic organs to only 16% and 17%, respectively, of the control levels. S-4 (3, 10 mg/kg) and DHT (3 mg/kg) restored castration-induced loss in lean body mass. Furthermore, S-4 treatment caused a significantly larger increase in total body bone mineral density (BMD) than DHT. S-4 (3 and 10 mg/kg) also demonstrated agonist activity in the pituitary, and significantly decreased plasma LH and FSH levels in castrated animals in a dose dependent manner. In summary, the strong anabolic effects of S-4 in skeletal muscle, bone, and pituitary were achieved with minimal pharmacologic effect in the prostate. The tissue selective pharmacologic activity of SARMs provides obvious advantages over steroidal androgen therapy and demonstrates the promising therapeutic utility that this new class of drugs may hold.

A Selective Androgen Receptor Modulator (SARM) for Hormonal Male Contraception
Jiyun Chen 1, Dong Jin Hwang 2, Casey E. Bohl 1, Duane D. Miller 2, James T. Dalton 1*

1 Division of Pharmaceutics, College of Pharmacy, The Ohio State University 2 Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis

Abstract

The recent discovery of nonsteroidal selective androgen receptor modulators (SARMs) provides a promising alternative for testosterone replacement therapies, including hormonal male contraception. The identification of an orally bioavailable SARM with the ability to mimic the central and peripheral androgenic and anabolic effects of testosterone would represent an important step toward the "male pill". We characterized the in vitro and in vivo pharmacologic activity of (S)-3-(4-Chloro-3-fluorophenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethylphenyl)propionamide ( C-6), a novel SARM developed in our laboratories. C-6 was identified as an androgen receptor (AR) agonist with high AR binding affinity (Ki = 4.9 nM). C-6 showed tissue-selective pharmacologic activity with higher anabolic activity than androgenic activity in male rats. The dose required to maintain the weight of the prostate, seminal vesicles, and levator ani muscle to one-half of the size of the maximum effects (i.e., ED50) was 0.78 ± 0.06, 0.88 ± 0.1 and 0.17 ± 0.04 mg/day, respectively. As opposed to other SARMs, gonadotropin levels in C-6-treated groups were significantly lower than control values. C-6 also significantly decreased serum testosterone concentration in intact rats after two weeks treatment. Marked suppression of spermatogenesis was observed after 10 weeks treatment with C-6 in intact male rats. Pharmacokinetic studies of C-6 in male rats revealed that C-6 was well absorbed after oral administration (bioavailability 76%), with a long (6.3 h) half-life at a dose of 10 mg/kg. These studies show that C-6 mimicked the in vivo pharmacologic and endocrine effects of testosterone while maintaining the oral bioavailability and tissue-selective actions of nonsteroidal SARMs.

Curr Opin Investig Drugs. 2006 Oct;7(10):873-81.Links
Selective androgen receptor modulators: in pursuit of tissue-selective androgens.
Omwancha J, Brown TR.

Johns Hopkins Bloomberg School of Public Health, Department of Biochemistry and Molecular Biology, Division of Reproductive Biology, 615 North Wolfe Street, Baltimore, MD 21205, USA.

The androgen receptor mediates the androgenic and anabolic activity of the endogenous steroids testosterone and 5alpha-dihydrotestosterone. Current knowledge of the androgen receptor protein structure, and the molecular mechanisms surrounding the binding properties and activities of agonists and antagonists has led to the design and development of novel nonsteroidal ligands with selected tissue-specific androgen receptor agonist and antagonist activities. The activity of these compounds, termed selective androgen receptor modulators (SARMs), is directed toward the maintenance or enhancement of anabolic effects on bone and muscle with minimal androgenic effects on prostate growth. SARMs are of potential therapeutic value in the treatment of male hypogonadism, osteoporosis, frailty and muscle wasting, burn injury and would healing, anemia, mood and depression, benign prostatic hyperplasia and prostate cancer.

J Musculoskelet Neuronal Interact. 2002 Mar;2(3):222-4.Links
Novel, non-steroidal, selective androgen receptor modulators (SARMs) with anabolic activity in bone and muscle and improved safety profile.
Rosen J, Negro-Vilar A.

Ligand Pharmaceuticals, San Diego, CA 92121, USA.

A novel approach to the treatment of osteoporosis in men, and possibly women, is the development of selective androgen receptor modulators (SARMs) that can stimulate formation of new bone with substantially diminished proliferative activity in the prostate, as well as reduced virilizing activity in women. Over the last several years, we have developed a program to discover and develop novel, non-steroidal, orally-active selective androgen receptor modulators (SARMs) that provide improved therapeutic benefits and reduce risk and side effects. In recent studies, we have used a skeletally mature orchiectomized (ORX) male rat as an animal model of male hypogonadism for assessing the efficacy of LGD2226, a nonsteroidal, non-aromatizable, and non-5alpha-reducible SARM. We assessed the activity of LGD2226 on bone turnover, bone mass and bone strength, and also evaluated the effects exerted on classic androgen-dependent targets, such as prostate, seminal vesicles and muscle. A substantial loss of bone density was observed in ORX animals, and this loss was prevented by SARMs, as well as standard androgens. Biochemical markers of bone turnover revealed an early increase of bone resorption in androgen-deficient rats that was repressed in ORX animals treated with the oral SARM, LGD2226, during a 4-month treatment period. Differences in architectural properties and bone strength were detected by histomorphometric and mechanical analyses, demonstrating beneficial effects of LGD2226 on bone quality in androgen-deficient rats. Histomorphometric analysis of cortical bone revealed distinct anabolic activity of LGD2226 in periosteal bone. LGD2226 was able to prevent bone loss and maintain bone quality in ORX rats by stimulating bone formation, while also inhibiting bone turnover. LGD2226 also exerted anabolic activity on the levator ani muscle. Taken together, these results suggest that orally-active, non-steroidal SARMs may be useful therapeutics for both muscle and bone in elderly hypogonadal men through their anabolic activities. Since SARMs both prevent bone loss, and also stimulate formation of new bone, they may have significant advantages relative to currently used anti-resorptive therapies. Coupled with their activity in muscle and their ability to maintain or restore libido, they offer new therapeutic approaches for male and female hormone replacement.
Click to expand...



estrogens increase bone formations too, shall we label them SARMs as well?

MOD EDIT: Stop the insults.
 
rms80 said:
I looked over the research some more this morning- and PA raised a couple of valid points- Icariin resembles a SERM as far as receptor binding- yet delivers effects that closely resemble those of a SARM- take a look:

A novel anticancer agent, icaritin, induced cell growth inhibition, G1 arrest and mitochondrial transmembrane potential drop in human prostate carcinoma PC-3 cells.




Icariin and icaritin with prenyl group have been demonstrated for their selective estrogen receptor modulating activities. We screened their effects on cell growth in human prostate carcinoma PC-3 cell line (estrogen receptor positive) in vitro. PC-3 cell line was used for the measurement of anti-carcinoma activities of 0-100 micromol/l icaritin and 30 micromol/l icariin. 1 micromol/l 17-beta estradiol (E(2)) served as the estrogen positive control, and 1 micromol/l ICI 182,780 [7 alpha-[9 (4,4,5,5,5-pentafluoropentyl) sulfinyl] nonyl]-estra-1,3,5(10)-triene-3,17h-diol]] served as the specific estrogen receptor antagonist. Primary cultured rat prostate basal cells used as cell growth selective control. The growth-inhibitory effects were analyzed using MTT assay, and fluorochrome staining, flow cytometry, and immunoblotting were employed to illustrate the possible mechanisms. When treated with icaritin for 24 to 72 h, cell growth was strongly inhibited (at 48 h IC(50) was 10.74+/-1.59 micromol/l, P<0.001) companied with a mitochondrial transmembrane potential (_Psim) drop. Meanwhile, few changes in IC(50) could be observed when co-incubated with ICI 182,780. Icaritin-induced growth inhibition was associated with G(1) arrest (P<0.05), and G(2)-M arrest depending upon doses. Consistently with G(1) arrest, icaritin increased protein expressions of pRb, p27(Kip1) and p16(Ink4a), while showed decrease in phosphorylated pRb, Cyclin D1 and CDK4. Comparatively, icariin has much lower effects on PC-3 cells and showed only weak G(1) arrest, suggesting a possible structure-activity relationship. These findings suggested a novel anticancer efficacy of icaritin mediated selectively via induction of cell cycle arrest but not associated with estrogen receptors in PC-3 cells.


Yet icariin (unlike a lot of other epimedium-based metabolites) exhibits no actual estrogenic activity:

Taxonomic, genetic, chemical and estrogenic characteristics of Epimedium species.

A


To understand the factors contributing to estrogenic properties of extracts from the genus Epimedium L. (Berberidaceae), we performed taxonomic, genetic and chemical characterization on 37 specimens from 18 species and related these to estrogen receptor (ERalpha and ERbeta) bioactivity, as measured by reporter genes in stable human cells. Boot strap values derived from amplified fragment length polymorphisms indicated that specimens of E. koreanum, E. brevicornum, E. myrianthum, E. leishanense, and E. membranaceum were genetically distinct and this was supported by their very similar ERalpha activities. In contrast, specimens from E. pubescens and E. sagittatum were diverse both genetically, chemically and in terms of ERalpha and ERbeta bioactivities. Strikingly, a genetic cluster comprising six rare Epimedium species exhibited strongest ERalpha and ERbeta activity, and this bioactivity was positively correlated with content of trace flavonoid aglycones (kaempferol, apigenin, quercetin, luteolin and breviflavone B). In contrast, there was no association between estrogenic activity and the major flavonol glycoside constituents (icariin and epimedin A-C). Although they exhibited equally strong ERalpha and ERbeta activity, E. koreanum can be clearly differentiated from E. pubescens and E. brevicornum by genetic distance and its significantly lower content of epimedin C. Our morphologic, genetic, chemical and bioactivity profiling provide the basis for the production of extracts with reproducible estrogenic properties. Such reproducibility will be critical for the standardization of Epimedium-based products.


Icariin has been shown to increase sexual drive and erectile function, both anecdotally and through research, and to also have testosterone mimetic effects, while not increasing estrogen.

Here is a study on men with Toremifene, another SERM:

The beneficial effects of toremifene administration on the hypothalamic-pituitary-testicular axis and sperm parameters in men with idiopathic oligozoospermia.

OBJECTIVE: To evaluate whether toremifene, a selective estrogen receptor modulator (SERM), has a beneficiary effect on all three main sperm parameters. DESIGN: Prospective interventional clinical study. SETTING: University hospital. PATIENT(S): One-hundred subfertile men with idiopathic oligozospermia. INTERVENTION(S): Toremifene (60 mg daily) was administered to all men for 3 months. At baseline and at the end of each month, serum concentrations of follicle-stimulating hormone (FSH), testosterone, inhibin B, and sex hormone-binding globulin (SHBG) were measured. At baseline and at the end, semen analysis was performed and sperm concentration, spermatozoal motility and normal sperm forms were determined. MAIN OUTCOME MEASURE(S): Gonadotropin, testosterone, inhibin-B levels, total sperm count, sperm morphology and motility. RESULT(S): Toremifene administration resulted in a significant increase in FSH, testosterone, SHBG, and inhibin B levels, as well as in sperm concentration, percentage motility and normal sperm forms. Twenty-two men's partners achieved pregnancy within 2 months of the end of treatment. At the end of the third month, serum FSH levels were significantly higher in the men whose partners did not achieve pregnancy, and total sperm count and normal sperm forms were significantly lower compared with the group of men whose partners achieved pregnancy. CONCLUSION(S): Toremifene administration for a period of 3 months in men with idiopathic oligozoospermia is associated with significant improvements of sperm count, motility, and morphology, mediated by increased gonadotropin secretion and possibly a direct beneficial effect of toremifene on the testes. The above findings are also indicative of a better testicular exocrine (improved sperm parameters) response to treatment in men whose partners achieved pregnancy compared with those who did not. Further randomized, placebo-controlled trials should be conducted to determine whether this particular selective estrogen receptor modulator can be useful as an initial approach in men with oligozoospermia.

SERMs and SARMs seem to have a lot of overlapping effects, especially in men- and icariin has effects that closely resemble both classes of compounds- icariin acts more like a conventional SERM with some characteristics, but more like a SARM with others.....
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it has nothing to do with a SARM and stop saying that. A SARM binds to and activates an androgen receptor. Icariin has one or two studies suggesting it raises endogenous testosterone

i might as well call 6-OXO a SARM.

you are using the word SARM because it is a hot buzz word now, and then finding indirect causational properties as some sort of evidence

its like me saying that pamela anderson brushes her teeth in the morning and so does Larry King, therefore Larry King is a hot chick
 
well i guess resveratrol is a SARM / SERM hybrid too according to your definition......









.....NOT (borat)



J Nutr Biochem. 2005 Aug;16(8):449-66. Links
Resveratrol as an anticancer nutrient: molecular basis, open questions and promises.Signorelli P, Ghidoni R.
Laboratory of Biochemistry and Molecular Biology, San Paolo University Hospital, School of Medicine, University of Milan, 20142 Milan, Italy.

The polyphenol resveratrol is an anticancer nutrient that was shown to inhibit cancer initiation and promotion [Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 1997;275:218-20]. The absorption, transport and metabolism of resveratrol will be reviewed as well as its actions in multiple pathways involved in the regulation of the cell cycle and the induction of apoptosis.................................................................................................................. ................................................................................................................................................................................................................Resveratrol acts as a selective estrogen receptor modulator (SERM) and regulates proteins involved in DNA synthesis and cell cycle, such as p(53) and Rb/E2F, cyclins, cyclin-dependent kinases (CDKs) and their inhibitors...............................................................................................................................................................................................................................................................................................................................................Resveratrol affects the activity of transcriptional factors involved in proliferation and stress responses, such as NF-kB, AP1 and Egr1. Part of these events is mediated by mitogen-activated protein kinases (MAPKs) and tyrosine kinases (e.g., Src) and leads to the modulation of survival and apoptotic factors [e.g., Bcl2 family members, inhibitors of apoptosis (IAPs), ceramide] as well as enzymes involved in carcinogenesis [cyclooxygenases (COXs), nitric oxide synthase (NOS), phase I and II enzymes]. Moreover, resveratrol affects the expression and the activity of cotranscriptional factors such as p(300) and sirtuin 1. Thus, resveratrol potential as an anticancer chemopreventive and chemotherapeutic agent and its implication in the prosurvival versus prodeath pathway induction will be discussed.

PMID: 16043028 [PubMed - indexed for MEDLINE]





J Nutr. 2005 Apr;135(4):757-60. Links
trans-Resveratrol, a natural antioxidant from grapes, increases sperm output in healthy rats.Juan ME, González-Pons E, Munuera T, Ballester J, Rodríguez-Gil JE, Planas JM.
Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, E-08028 Barcelona, Spain.

trans-Resveratrol was reported to have health benefits including anticarcinogenic effects and protection against cardiovascular disease. One of the mechanisms by which it exerts its action is through modulating the estrogen response systems. Because estrogen is involved in male reproductive biology, we investigated the effect of trans-resveratrol on testis and spermatogenesis. Adult male rats were divided into 2 groups. The treated group was administered by gavage 20 mg/(kg . d) of trans-resveratrol suspended in 10 g/L of carboxymethylcellulose for 90 d, whereas the control group received only carboxymethylcellulose during the same period. The relative weight of testes did not differ between the groups. However, the diameter of the seminiferous tubules was significantly reduced from 437.5 +/- 0.1 mum in the controls to 310.9 +/- 0.1 mum in the resveratrol-treated rats. This decrease was accompanied by a significant increase in tubular density, from 3.20 +/- 0.18 in controls to 6.58 +/- 0.18 tubules/mm(2) in the treated group. Moreover, sperm counts were significantly greater in the resveratrol-treated rats (24.8 +/- 3.30 x 10(7)) than in the control group (14.1 +/- 0.80 x 10(7)), but sperm quality did not differ..................................................................................................................................................................... Serum concentrations of gonadotrophins and testosterone were significantly higher in the resveratrol-treated group. We identified a novel activity of trans-resveratrol............................................................................................................................................................................... The daily oral administration of this phytochemical to adult male rats enhanced sperm production by stimulating the hypothalamic-pituitary-gonadal axis, without inducing adverse effects.

PMID: 15795430 [PubMed - indexed for MEDLINE]
 
Patrick Arnold said:
estrogens increase bone formations too, shall we label them SARMs as well?

MOD EDIT: Stop the insults.
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sorry

i woke up somewhat hungover and sleep deprived. and those stupid and completely misguided clapping hands piss me off

MOD EDIT: Deep breath. Count to 10. Look at porn. Smile.
 
Patrick Arnold said:
sorry

i woke up somewhat hungover and sleep deprived. and those stupid and completely misguided clapping hands piss me off

MOD EDIT: Deep breath. Count to 10. Look at porn. Smile.
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They seem to share some overlap- yes, icariin acts more like a SERM, but it does have some overlapping characteristics- would you be more happy with RPM being called "SERM-like with some SARM-like characteristics?"

Pat, I am not here to throw insults back and forth- I am simply giving my thought processes behind my claims- if you feel it is specious reasoning, understandable, but I don't find it to be. This is like a Venn Diagram- there are certain characteristics that icariin shares with SERMs, but some it does not, and there are certain characteristics that icariin shares with SARMs, and they overlap on both sides- on the receptor-binding level, icariin seems to resemble a SERM, but most SERMs do have some sort of effect on estrogen/estrogenic tissue- icariin does not seem to....I am sure you will argue with me and that is ok- I have stated my position, you have stated yours......
 
rms80 said:
They seem to share some overlap- yes, icariin acts more like a SERM, but it does have some overlapping characteristics- would you be more happy with RPM being called "SERM-like with some SARM-like characteristics?"

Pat, I am not here to throw insults back and forth- I am simply giving my thought processes behind my claims- if you feel it is specious reasoning, understandable, but I don't find it to be. This is like a Venn Diagram- there are certain characteristics that icariin shares with SERMs, but some it does not, and there are certain characteristics that icariin shares with SARMs, and they overlap on both sides- on the receptor-binding level, icariin seems to resemble a SERM, but most SERMs do have some sort of effect on estrogen/estrogenic tissue- icariin does not seem to....I am sure you will argue with me and that is ok- I have stated my position, you have stated yours......
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the SERM thing has validity, there is evidence of such agonist/antagonist activity (just like with practically every flavonoid - no great news here)

as far as the SARM claim goes, once again, you cannot classify two things together just because they share some downstream characteristics

refer to the pamela anderson analogy.

you must go by the definition. you are ignoring the definition and making deductions based on the fact that icariin might raise testosterone, affects bone integrity etc.
 
xjsynx said:
Guys? You mean guy. I am one person who speaks for himself.

But seriously, you calling me classy? What is next Michael Vick going to log in and say you shouldn't abuse animals?
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i never claimed to be classy

the truth is never pretty or slick
 
XJsynx, you crack my **** up.

As far as I'm concerned AN is done with this thread. It's going nowhere fast, and seems to be just another in a string of similar threads. Many of you catch my drift.

PA, I have a LOT of respect for your knowledge and expertise..... but just wish you'd apply it in a more productive manner sometimes. That's my personal opinion, that some will disagree with. Take no offense please, as I am sure you disagree. I apologize that someone started a thread that compared one of your products to RPM. AMP is a winner, IMO :clap2: (sorry, couldn't help adding in the hands)
 
Lanbane said:
XJsynx, you crack my **** up.

As far as I'm concerned AN is done with this thread. It's going nowhere fast, and seems to be just another in a string of similar threads. Many of you catch my drift.

PA, I have a LOT of respect for your knowledge and expertise..... but just wish you'd apply it in a more productive manner sometimes. That's my personal opinion, that some will disagree with. Take no offense, as I am sure you disagree. I apologize that someone started a thread that compared one of your products to RPM. AMP is a winner, IMO :clap2: (sorry, couldn't help adding in the hands)
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well i think me doing this from time to time is productive. out of line marketing needs to be addressed. if my marketing were out of line i would understand if i were called out on it.

its not like i am saying your product sucks, its probably good. there are tons of great products out there and some even don't have the name ergopharm on them!!
 
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