FW Friedel
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Behold- The Fat Free Tech Write-Up
- Thread starter rms80
- Start date
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FW Friedel
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FW Friedel
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OrganicShadow
Well-known member
Nice weekend read waiting for Superbowl to start. Some pretty pictures too.
This write up enlightens important information about the function of Ursolic Acid and how the chosen components to this product not only have their own MOA but how each process positively influence the others.
This write up enlightens important information about the function of Ursolic Acid and how the chosen components to this product not only have their own MOA but how each process positively influence the others.
JudoJosh
Pro Virili Parte
Go GIANTS!
madchemist
Banned
madchemist
Banned
it says in the article (which i can't copy since it's an image) post #52
[paraphrasing]
The article:
1) r-beta methyl PEA can cause the release of dopamine from nerve endings and the dopamine is then converted to NE
2) beta2 receptors promote smooth muscle relaxation and is stimulated by norepinephrine
3) hordenine is a NE reuptake inhibitor
The reality:
1) PEA can indeed act as a weak releasing agent, but its ability to induce substantial dopamine release is confined to the brain
a) <1% of peripheral sympathetic nerves release dopamine; 90% is released as NE, and ~4% as EP
b) PEA is a competitive inhibitor of dopamine beta-hydroxylase, and would actually retard conversion from dopamine to NE
c) the adrenal medulla releases 60% EP 39% NE and <1% DA
d) PEA has nothing to do with fat loss, and is a false neurotransmitter with zero receptor affinity in addition to its ability to block dopamine beta-hydroxylase
2) NE has substantially less activity at the beta2 receptor then epinephrine
a) en vivo (except coronary vessles), NE has nearly zero beta2 receptor activation
b) if you inject a giant IV bolus of NE, you will witness vasoconstriction due to alpha1, and an increase in plasma glycerol, also due to alpha1
3) hordenine has no appreciable affinity for blocking the NE transporter
a) en vitro, hordenine has about half the NE blockade potential of PEA and octopamine - neither of which have any real activity
b) hordenines only claim to fame is its ability to competitively inhibit MAOB; although its ability to do so is negligable since its metabolism is almost instantaneous; hordenine is bunk
[paraphrasing]
The article:
1) r-beta methyl PEA can cause the release of dopamine from nerve endings and the dopamine is then converted to NE
2) beta2 receptors promote smooth muscle relaxation and is stimulated by norepinephrine
3) hordenine is a NE reuptake inhibitor
The reality:
1) PEA can indeed act as a weak releasing agent, but its ability to induce substantial dopamine release is confined to the brain
a) <1% of peripheral sympathetic nerves release dopamine; 90% is released as NE, and ~4% as EP
b) PEA is a competitive inhibitor of dopamine beta-hydroxylase, and would actually retard conversion from dopamine to NE
c) the adrenal medulla releases 60% EP 39% NE and <1% DA
d) PEA has nothing to do with fat loss, and is a false neurotransmitter with zero receptor affinity in addition to its ability to block dopamine beta-hydroxylase
2) NE has substantially less activity at the beta2 receptor then epinephrine
a) en vivo (except coronary vessles), NE has nearly zero beta2 receptor activation
b) if you inject a giant IV bolus of NE, you will witness vasoconstriction due to alpha1, and an increase in plasma glycerol, also due to alpha1
3) hordenine has no appreciable affinity for blocking the NE transporter
a) en vitro, hordenine has about half the NE blockade potential of PEA and octopamine - neither of which have any real activity
b) hordenines only claim to fame is its ability to competitively inhibit MAOB; although its ability to do so is negligable since its metabolism is almost instantaneous; hordenine is bunk
OrganicShadow
Well-known member
The way I understand it is UA becomes more efficient when IGF-1 is high. The addition of DHEA has 2 fold function in the prevention of adrenal fatigue and positively influencing IGF levels. I heard of people running huge doses of UA but its more about the overall body biochemistry than the quantity that makes it effective. Also may have anti-aging benifits (George jumps up and shouts "Horay!")
Tobydog777
New member
rms80
Board Sponsor
Understood on the points you have made- there are better choices out there- you are welcome to disagree with my claims, but I don't really see the point in coming in the thread and acting downright disrespectful
rms80
Board Sponsor
My responses are in bold- you raise some interesting points- but in the section about norepinephrine, green coffee bean (extracted for caffeine) is included along with the R-Beta Methyl PEA, so some of these claimed characteristics do apply to caffeine....
it says in the article (which i can't copy since it's an image) post #52
[paraphrasing]
The article:
1) r-beta methyl PEA can cause the release of dopamine from nerve endings and the dopamine is then converted to NE
2) beta2 receptors promote smooth muscle relaxation and is stimulated by norepinephrine
3) hordenine is a NE reuptake inhibitor- once again, you may disagree w/ me, my sources are animal studies- see below
The reality:
1) PEA can indeed act as a weak releasing agent, but its ability to induce substantial dopamine release is confined to the brain Understood
a) <1% of peripheral sympathetic nerves release dopamine; 90% is released as NE, and ~4% as EP This is correct
b) PEA is a competitive inhibitor of dopamine beta-hydroxylase, and would actually retard conversion from dopamine to NE- you are correct, but theophylline (a component of caffeine that is coverted via P450) raises plasma DBH; unfortunately I am not really sure how the overall level of DBH would play out without some type further testing; because the formulation contains both entities and I am not sure to what extent the competitive inhibition would be overcome or how much of a factor it would be
c) the adrenal medulla releases 60% EP 39% NE and <1% DA Also correct
d) PEA has nothing to do with fat loss, and is a false neurotransmitter with zero receptor affinity in addition to its ability to block dopamine beta- hydroxylase I have to get back to you on this- I have limited time today
2) NE has substantially less activity at the beta2 receptor then epinephrine Absolutely
a) en vivo (except coronary vessles), NE has nearly zero beta2 receptor activation This is true
b) if you inject a giant IV bolus of NE, you will witness vasoconstriction due to alpha1, and an increase in plasma glycerol, also due to alpha1
True as well; Unfortunately, I used NE and E synonymously in the write-up when they are two different entities- I brain farted, my apologies- it is 25 pages long....I probably should go back and change it- thx for the heads' up
3) hordenine has no appreciable affinity for blocking the NE transporter
a) en vitro, hordenine has about half the NE blockade potential of PEA and octopamine - neither of which have any real activity
b) hordenines only claim to fame is its ability to competitively inhibit MAOB; although its ability to do so is negligable since its metabolism is almost instantaneous; hordenine is bunk Below are the animal studies from which I derived my information; I acknowledge that humans and animals may have very different physiological reactions
Dtsch Tierarztl Wochenschr. 1995 Jun;102(6):228-32.
[Pharmacological effects of hordenine].
[Article in German]
Invalid Link Removed, Invalid Link Removed.
Source
Institut für Pharmakologie, Toxikologie und Pharmazie, Tierärztlichen Hochschule Hannover.
Abstract
Hordenine is an ingredient of some plants which are used as feed for animals, i.e. in sprouting barley. After ingestion of such feed hordenine may be detected in blood or urine of horses which in case of racing horses may be the facts of using prohibited compounds. Results of some experiments in pharmacological models show that hordenine is an indirectly acting adrenergic drug. It liberates norepinephrine from stores. In isolated organs and those structures with reduced epinephrine contents the hordenine-effect is only very poor. Experiments in intact animals (rats, dogs) show that hordenine has a positive inotropic effect upon the heart, increases systolic and diastolic blood pressure, peripheral blood flow volume, inhibits gut movements but has no effect upon the psychomotorical behaviour of mice. All effects are short and only possible after high doses which are not to be expected after ingestion of hordenine containing feed for horses. A measurable increase of the performance of racing horses is quite improbable.
J Pharm Pharmacol. 1989 Jun;41(6):421-3.
Deamination of hordenine by monoamine oxidase and its action on vasa deferentia of the rat.
Invalid Link Removed, Invalid Link Removed, Invalid Link Removed, Invalid Link Removed.
Source
School of Pharmacy, Portsmouth Polytechnic, Hampshire, UK.
Abstract
The selectivity of the naturally occurring amine, N,N-dimethyltyramine (hordenine) for monoamine oxidase (MAO) and its action upon isolated vasa deferentia of the rat was investigated. Hordenine was deaminated by rat liver MAO with a Michaelis constant of 479 microM and maximum velocity of 128 nmol (mg protein)-1 h-1 compared with 144 microM and 482 nmol (mg protein)-1 h-1 for tyramine. Studies, with selective irreversible inhibitors of MAO, showed that hordenine was a highly selective substrate for MAO-B of liver and that it was not deaminated by the MAO-A of intestinal epithelium. In contrast to tyramine, hordenine did not produce contractions of isolated vasa deferentia. However, 25 microM hordenine potentiated contractile responses of vasa, from control animals, to submaximal doses of noradrenaline and inhibited responses to tyramine. It did not alter responses, to noradrenaline, of vasa denervated by chronic pretreatment of rats with guanethidine. Therefore, it appears that hordenine acted as an inhibitor of noradrenaline uptake, in isolated vasa deferentia. These results indicate that dietary-hordenine is unlikely to be deaminated by intestinal MAO as this is predominantly MAO-A. Consequently, it is likely to be absorbed and could affect the sympathetic nervous system, by virtue of its action as an inhibitor of noradrenaline uptake.
it says in the article (which i can't copy since it's an image) post #52
[paraphrasing]
The article:
1) r-beta methyl PEA can cause the release of dopamine from nerve endings and the dopamine is then converted to NE
2) beta2 receptors promote smooth muscle relaxation and is stimulated by norepinephrine
3) hordenine is a NE reuptake inhibitor- once again, you may disagree w/ me, my sources are animal studies- see below
The reality:
1) PEA can indeed act as a weak releasing agent, but its ability to induce substantial dopamine release is confined to the brain Understood
a) <1% of peripheral sympathetic nerves release dopamine; 90% is released as NE, and ~4% as EP This is correct
b) PEA is a competitive inhibitor of dopamine beta-hydroxylase, and would actually retard conversion from dopamine to NE- you are correct, but theophylline (a component of caffeine that is coverted via P450) raises plasma DBH; unfortunately I am not really sure how the overall level of DBH would play out without some type further testing; because the formulation contains both entities and I am not sure to what extent the competitive inhibition would be overcome or how much of a factor it would be
c) the adrenal medulla releases 60% EP 39% NE and <1% DA Also correct
d) PEA has nothing to do with fat loss, and is a false neurotransmitter with zero receptor affinity in addition to its ability to block dopamine beta- hydroxylase I have to get back to you on this- I have limited time today
2) NE has substantially less activity at the beta2 receptor then epinephrine Absolutely
a) en vivo (except coronary vessles), NE has nearly zero beta2 receptor activation This is true
b) if you inject a giant IV bolus of NE, you will witness vasoconstriction due to alpha1, and an increase in plasma glycerol, also due to alpha1
True as well; Unfortunately, I used NE and E synonymously in the write-up when they are two different entities- I brain farted, my apologies- it is 25 pages long....I probably should go back and change it- thx for the heads' up
3) hordenine has no appreciable affinity for blocking the NE transporter
a) en vitro, hordenine has about half the NE blockade potential of PEA and octopamine - neither of which have any real activity
b) hordenines only claim to fame is its ability to competitively inhibit MAOB; although its ability to do so is negligable since its metabolism is almost instantaneous; hordenine is bunk Below are the animal studies from which I derived my information; I acknowledge that humans and animals may have very different physiological reactions
Dtsch Tierarztl Wochenschr. 1995 Jun;102(6):228-32.
[Pharmacological effects of hordenine].
[Article in German]
Invalid Link Removed, Invalid Link Removed.
Source
Institut für Pharmakologie, Toxikologie und Pharmazie, Tierärztlichen Hochschule Hannover.
Abstract
Hordenine is an ingredient of some plants which are used as feed for animals, i.e. in sprouting barley. After ingestion of such feed hordenine may be detected in blood or urine of horses which in case of racing horses may be the facts of using prohibited compounds. Results of some experiments in pharmacological models show that hordenine is an indirectly acting adrenergic drug. It liberates norepinephrine from stores. In isolated organs and those structures with reduced epinephrine contents the hordenine-effect is only very poor. Experiments in intact animals (rats, dogs) show that hordenine has a positive inotropic effect upon the heart, increases systolic and diastolic blood pressure, peripheral blood flow volume, inhibits gut movements but has no effect upon the psychomotorical behaviour of mice. All effects are short and only possible after high doses which are not to be expected after ingestion of hordenine containing feed for horses. A measurable increase of the performance of racing horses is quite improbable.
J Pharm Pharmacol. 1989 Jun;41(6):421-3.
Deamination of hordenine by monoamine oxidase and its action on vasa deferentia of the rat.
Invalid Link Removed, Invalid Link Removed, Invalid Link Removed, Invalid Link Removed.
Source
School of Pharmacy, Portsmouth Polytechnic, Hampshire, UK.
Abstract
The selectivity of the naturally occurring amine, N,N-dimethyltyramine (hordenine) for monoamine oxidase (MAO) and its action upon isolated vasa deferentia of the rat was investigated. Hordenine was deaminated by rat liver MAO with a Michaelis constant of 479 microM and maximum velocity of 128 nmol (mg protein)-1 h-1 compared with 144 microM and 482 nmol (mg protein)-1 h-1 for tyramine. Studies, with selective irreversible inhibitors of MAO, showed that hordenine was a highly selective substrate for MAO-B of liver and that it was not deaminated by the MAO-A of intestinal epithelium. In contrast to tyramine, hordenine did not produce contractions of isolated vasa deferentia. However, 25 microM hordenine potentiated contractile responses of vasa, from control animals, to submaximal doses of noradrenaline and inhibited responses to tyramine. It did not alter responses, to noradrenaline, of vasa denervated by chronic pretreatment of rats with guanethidine. Therefore, it appears that hordenine acted as an inhibitor of noradrenaline uptake, in isolated vasa deferentia. These results indicate that dietary-hordenine is unlikely to be deaminated by intestinal MAO as this is predominantly MAO-A. Consequently, it is likely to be absorbed and could affect the sympathetic nervous system, by virtue of its action as an inhibitor of noradrenaline uptake.
rms80
Board Sponsor
Actually good questions- oral bioavaliability of DHEA isn't great, but serviceable- the amount included will do the task intended, at least according to the dosage studies that I have seen. As for estro levels- may increase slightly, but not to the point where any type of intervention strategy is needed; I wouldn't worry about DHT on this product, either. And yes, I would run it Free Test and/or HGH-Up- should stack in really well. To answer the 3rd question- I would take 1-2 grams of tyrosine a day post-product or Revamp.....
chedapalooza
Legend
madchemist said:
Thanks man, have a great weekend lol
rms80
Board Sponsor
This is a link the study from which I derived much of my info about PEA + MAO-Inhibitors:
Invalid Link Removed
It is a bit of a read, but is pretty in-depth when it comes to the psychomotor and pharmalogical responses to the combo.....would have posted this earlier, but it was saved in my laptop, not my phone....
Invalid Link Removed
It is a bit of a read, but is pretty in-depth when it comes to the psychomotor and pharmalogical responses to the combo.....would have posted this earlier, but it was saved in my laptop, not my phone....
madchemist
Banned
not sure what that's trying to prove, but nothing in your formula is even in the same league as deprenyl. the main brain location that PEA influences dopamine release in humans is in the striatum, which has to do with movement. even if it had a huge dopamine response in the ventral tegmental area (which is what that article is referencing), it would have almost nothing to do with fat loss.
rms80
Board Sponsor
The reason for posting this was to show where my thought process was coming from- unfortunately deprenyl isn't avaliable as an ingredient to put in an OTC product, and the scope of potentially DSHEA-compliant ingredients that act as MAO inhibitors is somewhat slim. Hordenine does act to inhibit MAO, albeit weakly. The research demonstrates MAOI + PEA demonstrates some effects similar to amphetamine, outside of the brain. PEA + an MAOI does not equal amphetamine, but the study shows that there are some similarities.
Several Questions:
1. Do you feel that a compound(s) acting by themselves, or in concert as an anorectic, would contribute to fat loss?
2. Why would there be a significant amount of studies on PEA for fat loss, when it is easily metabolized without some type of accompanying MAOI?
3. Chemically speaking, there are multiple similar compounds that are similar to PEA that do not need an accompanying MAOI to produce an appreciable anorectic effect (ie fenfulramine, amphetamine, benflourex, etc.). Would you or would you not study these first in terms of an avenue for fat loss?
4. Do you agree that patentable material will supercede non-patentable material over the course of research?
5. Do you feel that I would be a free man if I included some of the anorectic agents listed in 3, or a prescription MAOI, in my products, and that my manfacturing facility would still be able to conduct business?
6. Do you feel that PEA + an MAOI, having some similarities in physiological response to anorectics like amphetamine, could have an anorectic effect on users?
You have to get a little creative in this business- my hands are tied on certain avenues, so you have to go around your ass to get to your elbow sometimes, from a formulational standpoint. The answers to the above questions should give you why I chose what I chose- are they the best choices? From your standpoint, no, but from my standpoint I have to look at multiple angles:
1. Safety
2. Compliance- certain "hot" ingredients in the fat loss realm are getting a LOT of unwanted scrutiny ATM, but this formulation does not contain any of them
3. How the products fit in with the rest of the line
4. Can these ingredients be sourced from my normal suppliers? Or am I going to have to go to random multiple suppliers and constantly switch materials? Seeing as how I test everything that comes into our facility, this gets very difficult from QC standpoint, not to mention an analytical testing standpoint- I test materials constantly, and it gets to be a huge pain in the ass trying to build regression equations for multiple "versions" of the same ingredient.
5. Can the formulation be mass-manufactured and run optimally in our facility? 50% of a formulation is geting the actives functionally right, and 50% is being able to run it correctly on our machinery and have the blend spec test out according to our standards. This product wasn't easy, by any stretch of the imagination, for multiple reasons....
It isn't always just black and white.....there are a lot more angles that you didn't factor in- most company owners wouldn't even bother arguing any of these points, but I will- maybe you see my POV, maybe you don't- at this point I don't really expect you to- I have to take into account all of the following- all you have to do is trash the product- to me that isn't a very fair trade-off
madchemist
Banned
not sure if you've experimented with PEA + deprenyl
i have and it only makes the PEA buzz last a bit longer.
i see your point about DSHEA compliance, and wish you luck with this product. you seem like a nice guy so i wont continue to be a pain in your ass
i have and it only makes the PEA buzz last a bit longer.
i see your point about DSHEA compliance, and wish you luck with this product. you seem like a nice guy so i wont continue to be a pain in your ass
rms80
Board Sponsor
Thank you kindly, and you raise very valid points- I have taken deprenyl and PEA, and it is ok, but nothing special- the strongest combo I have found is PEA/Hord/modafinil- not sure of the exact reason why it works so well- modafinil is also poorly researched, and until a few years ago, they couldn't even pinpoint a direct mechanism of action for the compound (hard to believe, b/c it is FDA-approved). The effects are much longer acting, and are similar to amp w/o as much of a euphoric effect. R-Beta Methyl PEA (higher dose) plus hord has some relatively strong effects on appetite from what I have seen (and other people I have had test this combo), along with some amp-like effects (jawing/teeth-grinding, some euphoria, increased vigilance)- and to your point, there aren't any studies to confirm this, and there probably won't be- see below for my potential reasoning....
Believe it or not, because of your line of questions- I went back and did a few hours of extra research on this, and there is a time-dependant gap in the research, which I found interesting. The reason? Phen-fen and PPA, LOL. There are literally hundreds of studies in the area relating biogenic amines and MAOIs to anorectic effects and weight loss during the period of the mid-late 70's through the late 90's. Many of the drugs they focused heavily on (Phenterine, fenfluramine, DMI, PPA) were later linked to some serious health issues- once the lawsuits started to fly, research in this of weight loss virtually stopped- and they definitely threw the baby out with the bath water, b/c there are some combos/compounds in this area that could be of significant potential to SAFE weight loss, but no IRB in its right mind would touch b/c of the potential legal ramifications- this is most likely why there are mostly only animal studies post-1999 in this particular area
rms80
Board Sponsor
Thx bro