Compound 20

[rome32]

Are you joking? Another personal attack? I DID PM you about the science. You never responded but continue to insult me publicly. Absolutely classless. And please don't pretend like you can school me in the subject at hand.

This isn't the high school locker room. You own a company and carry yourself like this? I said it earlier and I'll say it again: Grow Up.

I didn't take it as a personal attack. I agree with USPowders. I think he is justified.

 

[mr.cooper69]

I didn't take it as a personal attack. I agree with USPowders. I think he is justified.

You're entitled to your opinion; I take no issue with you. It is also quite clear that paragraph 2 of his post is a personal attack. Please note that I want nothing to do with this thread out of respect for USPlabs but HE keeps it bumped and keeps the attacks rolling...

 

[jbryand101b]

I can knock a product without trying it.

But why all the fuss? it isn't a androgenic/anabolic steroid
Or a sarm.

 

[rome32]

You're entitled to your opinion; I take no issue with you. Please note that I want nothing to do with this thread out of respect for USPlabs but HE keeps it bumped and keeps the attacks rolling...

I understand. I see both sides to the issue. Let us let this one die. The amount of bombardment C20 has gotten lately would anger me as well if I worked/owned the company.

No hard feelings towards anyone. We all just need to work on presenting ourselves a little better. Month ago I blew up on you and I apologize now for it. We can all move foreward now. No more bashing or trashing on threads. Not saying you were just in general for everyone.

 

[USPlabsRep]

Are you joking? Another personal attack?

I DID PM you about the science, and I even put aside my pride and apologized in the PM. You never responded but continue to insult me publicly. Absolutely classless.

I'm in every Compound 20 thread, eh? I'll take your word for it.

What degrees do you have in science again? Because madchemist is qualified to give a university lecture about the subject at hand. And please don't pretend like you can school me in the subject either.

This isn't the high school locker room. You own a company and carry yourself like this? I said it earlier and I'll say it again: ​Grow Up.[/QUOT

I'm not a scientist nor do I pretend to be one. I defer to my research and develoment department. I have a degree in Clinical Nutrition.

Its become evident you don't like to be questioned and challenged. I'll back off right after a consumer statement. I welcome your response. Next post.

 

[Clemenza]

I agree. One simply can can not...

1. Knock a product without trying it to begin with.
2. Say if science or biochemistry can't prove it, it doesn't work.

Before I got serious into the forum game I took products based off customer feedback, not scientific facts, nor did I research product ingredients that weren't simple like arginine, glutamine, etc.

I believe a rep or a product owner should be able to defend their product. They feel as if it is their child and you all would do the same.
If, hypothetically, I made a post that SNS DAA caps did nothing for me and everything such as diet, dosing, training, etc were spot on. Would you say I am wrong because data proves it works? Get it? I would get attacked. Most likely from reps and other forum members who have tried said product.

Let us make an end to this sh*t...

I wanted to save it for my recomp, but I will log Compound 20 solo if it pleases the masses and ends this discussion. I started a log on the Carbonite Stack and someone tried to start drama on there about it. Made me sick to say the least...he never tried it.

So unless you personally take said product or ingredient please stop all this jibber jabber...all everyone wants to be is right in here rather than help, learn, and teach.

So who wants a log on Compound 20 solo?

I have a bottle Compound 20. I will log it solo starting next week, alongside you.

 

[rome32]

I have a bottle Compound 20. I will log it solo starting next week, alongside you.

Let's do it bro!

 

[mr.cooper69]

Its become evident you don't like to be questioned and challenged. I'll back off right after a consumer statement. I welcome your response. Next post.

I have no problem being questioned and challenged (see my discussions with dinoiii in the sub-forum). I could easily extend the same statement to you. I don't want to discuss this publicly because of the associated legal issues that could occur, hence why I PMed you. I already sent you my questions, and my PM box is open. I see no reason why we can't see eye-to-eye if a PM exchange proves useful.

 

[hanson8031]

wanted to save it for my recomp, but I will log Compound 20 solo if it pleases the masses and ends this discussion. I started a log on the Carbonite Stack and someone tried to start drama on there about it. Made me sick to say the least...he never tried it.


Hey man just wondering where you have this log posted at?

 

[rome32]

wanted to save it for my recomp, but I will log Compound 20 solo if it pleases the masses and ends this discussion. I started a log on the Carbonite Stack and someone tried to start drama on there about it. Made me sick to say the least...he never tried it.

Hey man just wondering where you have this log posted at?

Meant thread lol thanks for catching that for me! I believe a user named breezy(some numbers I dont remember) has a log.

Mine was a thread asking who was thinking about picking it up and some guy chimed in and started drama and said he never tried it, but it won't work. Irritating.

 

[hanson8031]

Alright man thanks! I'll look for it. Thinking about taking this and have seen a lot of mixed emotions on it so just trying to read up a little more

 

[rome32]

Alright man thanks! I'll look for it. Thinking about taking this and have seen a lot of mixed emotions on it so just trying to read up a little more

Def. No problemo.

If you're interested in a lean/bulk check the log in my signature too

 

[JudoJosh]

Lol I said I didn't want drama, hence why I let this thread die to begin with.

I completely understand this as I do it all the time. Debating on forums can be quite a frustrating and futile endeavor.

From my experience on these boards it is best to just present the information and evidence for your opinion and then walk away. Trying to change someones mind is very difficult (i.e try explaining to someone they dont need an immediate post workout gi spike or that dietary intake of saturated fat isnt bad for you) so instead of trying to convince someone I merely preset my opinion and supporting evidence for the rest of the community to see, and walk away. They either accept it or dont. You will go crazy trying to change everyones mind and it just isnt worth it, especially considering how often the same questions and topics are brought up in these boards.

 

[Whacked]

I need to adopt this logic quick before my blood pressure spirals out of control

I completely understand this as I do it all the time. Debating on forums can be quite a frustrating and futile endeavor.

From my experience on these boards it is best to just present the information and evidence for your opinion and then walk away. Trying to change someones mind is very difficult (i.e try explaining to someone they dont need an immediate post workout gi spike or that dietary intake of saturated fat isnt bad for you) so instead of trying to convince someone I merely preset my opinion and supporting evidence for the rest of the community to see, and walk away. They either accept it or dont. You will go crazy trying to change everyones mind and it just isnt worth it, especially considering how often the same questions and topics are brought up in these boards.

 

[LiveToLift]

Funny this just keeps on going... Think there's 4 threads attacking this product now, I feel for you USP but hey you sure are popular!

 

[DCbuilder]

....I don't want to discuss this publicly because of the associated legal issues that could occur, hence why I PMed you.....

How could posting info on the science behind an ingredient cause a legal issue?

 

[Whacked]

That's not what he is referring to.

We would ALL love for the science to be posted

How could posting info on the science behind an ingredient cause a legal issue?

 

[Whacked]

And why do you think that is?

No one has an agenda agaisnt USP.....only questions. That's all. See above post.

Funny this just keeps on going... Think there's 4 threads attacking this product now, I feel for you USP but hey you sure are popular!

 

[LiveToLift]

And why do you think that is?

No one has an agenda agaisnt USP.....only questions. That's all. See above post.

Honestly I had no interest in flaring up your out burst hence why I left you out of it! Just noting that the product will never fully be liked by those who aren't willing to try it... I think its funny at how you go about things after the godfather himself Mr. Dunn commented on how poorly you handle yourself. :-D Have a great day!

Edit: I was one of those low post count guys that whacked was talking about pages back....

 

[AaronJP1]

I miss something....
opcorn:

 

[LiveToLift]

I miss something....
opcorn:

Not at all, hopefully everything is finished here!

 

[Celorza]

I miss something....
opcorn:

Bunch of Immature posts IMO , and some wisdom shed by MrCooper , poor maners by the USP representative...and also a bit of "past ordeals" being quoted also...Can't an admin close/delete this thread so as to help it die already? Clearly people are gonna keep bumping it...sorry that I am doing so in a way too...but I think this has gone way past a mature stance and polite discussion by childish behavoirs from certain individuals.

(Just to calirify: I do not think MrCooper was wrong in any way...as far as I have read (and i read it all...) he has been mature and merely "touched" a nerve so it seems with the USP Man child...)

Sorry for being part of it...but lets just let it die ok?

 

[LiveToLift]

Bunch of Immature posts IMO , and some wisdom shed by MrCooper , poor maners by the USP representative...and also a bit of "past ordeals" being quoted also...Can't an admin close/delete this thread so as to help it die already? Clearly people are gonna keep bumping it...sorry that I am doing so in a way too...but I think this has gone way past a mature stance and polite discussion by childish behavoirs from certain individuals.

(Just to calirify: I do not think MrCooper was wrong in any way...as far as I have read (and i read it all...) he has been mature and merely "touched" a nerve so it seems with the USP Man child...)

Sorry for being part of it...but lets just let it die ok?

I highly doubt this "classy" post is going to help anything die. LMAO what a trip...

 

[Celorza]

I highly doubt this "classy" post is going to help anything die. LMAO what a trip...

I missed my chance at being classy I guess Oo the thing is...I dont really like how a suposedly grown man (USP) and company representative can be like that, when he got offered a branch of olives...a pm with even an apology and some mature discussion away form the public eye and need for attention...I get upset easily when i see that kinda thing ^^' But then again I AM quite immature myself...But i tend to try and respect others , specially if they are being respectful.

 

[FL3X MAGNUM]

Come on now guys.
This is getting everybody nowhere.
Unless a mod wants to come close this thread I think everyone should call it no contest and let the thread die (again).

 

[jbryand101b]

Come on now guys.
This is getting everybody nowhere.
Unless a mod wants to come close this thread I think everyone should call it no contest and let the thread die (again).

Compound 20 sucks, pink magic is da bomb yo, or do I hear.

Stack wid some sarmx an gakik for wyked gaynz

 

[FL3X MAGNUM]

Compound 20 sucks, pink magic is da bomb yo, or do I hear.

Stack wid some sarmx an gakik for wyked gaynz

Can't get Wyked anymore brah, Taurus be closing up shop.

 

[Geoforce]

I completely understand this as I do it all the time. Debating on forums can be quite a frustrating and futile endeavor.

From my experience on these boards it is best to just present the information and evidence for your opinion and then walk away. Trying to change someones mind is very difficult (i.e try explaining to someone they dont need an immediate post workout gi spike or that dietary intake of saturated fat isnt bad for you) so instead of trying to convince someone I merely preset my opinion and supporting evidence for the rest of the community to see, and walk away. They either accept it or dont. You will go crazy trying to change everyones mind and it just isnt worth it, especially considering how often the same questions and topics are brought up in these boards.

This could very well be stickied. I know I have borderline lost my mind at times on some boards. Which is odd cause I'm usually very calm and non-confrontational in real life. I guess it's just the internet argument syndrome and wanting to get the last word/be proven right. Reps for this one and spot on JJ.

 

[rome32]

This could very well be stickied. I know I have borderline lost my mind at times on some boards. Which is odd cause I'm usually very calm and non-confrontational in real life. I guess it's just the internet argument syndrome and wanting to get the last word/be proven right. Reps for this one and spot on JJ.

Word.

 

[Whacked]

Bro, I dont know you or have a clue what your beef is with me. LOL

PS: 2,210 is not a low post count so I have no clue what you're even referring to. When I refer to people with low posts counts that "magically appear", I am referring to those with 10-20 or less post that show up randomly and pimp products that have an obvious agrendas.

Take care

Honestly I had no interest in flaring up your out burst hence why I left you out of it! Just noting that the product will never fully be liked by those who aren't willing to try it... I think its funny at how you go about things after the godfather himself Mr. Dunn commented on how poorly you handle yourself. :-D Have a great day!

Edit: I was one of those low post count guys that whacked was talking about pages back....

 

[Whacked]

I concur Geo. What compels me to even reply is beyond me. Oh well, we all have our weaknesses.

This could very well be stickied. I know I have borderline lost my mind at times on some boards. Which is odd cause I'm usually very calm and non-confrontational in real life. I guess it's just the internet argument syndrome and wanting to get the last word/be proven right. Reps for this one and spot on JJ.

 

[neddo]

There's a reason many avoid USPLabs.

Thumbs up, Rep. Stay classy.

 

[USPlabsRep]

I want to leave the board with this explanation from our lead formulator and scientific consultant.
I can use this as an example. Ican point out plenty of molecules which make great substrates for COMT. I cango even further and point out that they were then confirmed in vivo to besubstrates of COMT (which, by the way, is not the only way these compounds aremetabolized as is nearly always the case) based upon urinary metabolites. Yet,simply being a good substrate for COMT does not equal 0% bioavailability. Itdoes not equal a 1 minute half-life. It does not mean, in any way, that it willhave the same pharmacokinetic properties as another compound, even if thestructural similarities are many; in fact stereoisomers (thus, structuralformula is not just similar but actually identical) of various compounds, includingsome beta 2-adrenoceptor agonists themselves, display substantial differencesin bioavailability and other pk parameters. This is why these parameters mustbe determined experimentally, period. This is why drug discovery departmentsdon't have a guy on a computer in the corner, google searching for similarlooking molecules, reviewing their pharmacokinetic properties and thenconcluding that the compound in question is probably the same, so they ditchit. You can form a hypothesis that they may be similar in that regard, but toknow for certain, you must investigate through experimentation. That is basicscience. Anything else is a prediction and will always remain so, period. Andany person that doesn't have an advanced scientific background that mightbelieve that such comparisons just make good enough sense that theirhypothesis, "just HAS to be right", should visit one of the severaljournal publications (i.e., negative result journals) that focus on nothing buthypotheses that were not supported by their experimental results. Of course, Ishould also point, most don't bother to ever publish such results, so let'sjust say the vast majority of hypotheses don't fit with the experimental dataand that's because we're human and we're studying what are arguably complexmatters where a multitude of variables aren't known and those that are may notbe taken into account.

In this particular case, simply being a substrate for a given enzyme whichserves to create inactive metabolites does not mean A) it can't be saturated B)that the amount produced is enough to yield none of the active base C) that itis the major route or the only route of metabolism and D) that it isn'tresistant to another route E) that all routes of metabolism produce onlyinactive metabolites as opposed to equipotent or even hyperpotent metabolitesF) It really does go on and on regarding potential variables at work here whichis why experimentation is vital.

In fact, we have a compound which we are investigating for potential futurerelease which has the catechol ring (thus it was supposed that it would likelybe a substrate for COMT) and yes, it does in fact undergo o-methylation to asubstantial degree, as it has been confirmed by determination of theo-methylated urinary (there's that experimentation part again). So, using thispredictive logic, this compound should be thrown in the trash despitedmetabolites emonstrating potent activity at the beta 2-adrenoceptor. Yet, whenactually investigating the oral bioavailability of this compound(experimentation), we find it is in the double digits. And we find thehalf-life isn't just 1 or 2 minutes but much, much longer. So, we have acompound that is a great substrate for COMT, yet still has pk characteristicsthat make it viable; this is why experimental data are important andsupposition is meaningless without it. Are these pk values ideal? Compared tomany pharmaceuticals, no (although, there are even some examples ofpharmaceutical compounds with less than ideal bioavailability values). But, wearen't a pharmaceutical company and this isn't the pharmaceutical industry. Ouronly similarity is with those pharmaceutical companies that still haveoperating sections of natural products drug discovery, only we generally haveto stop at the lead in most cases. But, often times, depending upon what thegoal is, the lead may in fact be good enough. I would also hope that mostunderstand that even the slightest change in a molecule can yield substantiallydivergent pharmacokinetic and pharmacodynamic properties.

In any case, this brings us to the next point which is that there is more toconsider aside from bioavailability and half-life. If a particular compoundpossesses the necessary potency at whatever your given molecular target may be,the bioavailability in particular may not be of much importance, especially ifthere is room for a variable dose. For example, if the concentration needed foractivity is in the picomolar or nanomolar range and the given compound yieldsserum concentrations in that range after administration of 1,000 mg or 3,000mg, what does it matter if the bioavailability is only 5%? The answer is thatit doesn't.

I think discussion is great and reviews like this are a great way to sparkexperimentation and improve study design, but let's be better than simplytaking a hypothesis and using it as a justification to say whether somethinghas value or not. In fact, if we want to respect science at all, let's not takehypotheses and use them as, "facts", which in reality, do not existto begin with.

 

[LiveToLift]

I want to leave the board with this explanation from our lead formulator and scientific consultant.
I can use this as an example. Ican point out plenty of molecules which make great substrates for COMT. I cango even further and point out that they were then confirmed in vivo to besubstrates of COMT (which, by the way, is not the only way these compounds aremetabolized as is nearly always the case) based upon urinary metabolites. Yet,simply being a good substrate for COMT does not equal 0% bioavailability. Itdoes not equal a 1 minute half-life. It does not mean, in any way, that it willhave the same pharmacokinetic properties as another compound, even if thestructural similarities are many; in fact stereoisomers (thus, structuralformula is not just similar but actually identical) of various compounds, includingsome beta 2-adrenoceptor agonists themselves, display substantial differencesin bioavailability and other pk parameters. This is why these parameters mustbe determined experimentally, period. This is why drug discovery departmentsdon't have a guy on a computer in the corner, google searching for similarlooking molecules, reviewing their pharmacokinetic properties and thenconcluding that the compound in question is probably the same, so they ditchit. You can form a hypothesis that they may be similar in that regard, but toknow for certain, you must investigate through experimentation. That is basicscience. Anything else is a prediction and will always remain so, period. Andany person that doesn't have an advanced scientific background that mightbelieve that such comparisons just make good enough sense that theirhypothesis, "just HAS to be right", should visit one of the severaljournal publications (i.e., negative result journals) that focus on nothing buthypotheses that were not supported by their experimental results. Of course, Ishould also point, most don't bother to ever publish such results, so let'sjust say the vast majority of hypotheses don't fit with the experimental dataand that's because we're human and we're studying what are arguably complexmatters where a multitude of variables aren't known and those that are may notbe taken into account.

In this particular case, simply being a substrate for a given enzyme whichserves to create inactive metabolites does not mean A) it can't be saturated B)that the amount produced is enough to yield none of the active base C) that itis the major route or the only route of metabolism and D) that it isn'tresistant to another route E) that all routes of metabolism produce onlyinactive metabolites as opposed to equipotent or even hyperpotent metabolitesF) It really does go on and on regarding potential variables at work here whichis why experimentation is vital.

In fact, we have a compound which we are investigating for potential futurerelease which has the catechol ring (thus it was supposed that it would likelybe a substrate for COMT) and yes, it does in fact undergo o-methylation to asubstantial degree, as it has been confirmed by determination of theo-methylated urinary (there's that experimentation part again). So, using thispredictive logic, this compound should be thrown in the trash despitedmetabolites emonstrating potent activity at the beta 2-adrenoceptor. Yet, whenactually investigating the oral bioavailability of this compound(experimentation), we find it is in the double digits. And we find thehalf-life isn't just 1 or 2 minutes but much, much longer. So, we have acompound that is a great substrate for COMT, yet still has pk characteristicsthat make it viable; this is why experimental data are important andsupposition is meaningless without it. Are these pk values ideal? Compared tomany pharmaceuticals, no (although, there are even some examples ofpharmaceutical compounds with less than ideal bioavailability values). But, wearen't a pharmaceutical company and this isn't the pharmaceutical industry. Ouronly similarity is with those pharmaceutical companies that still haveoperating sections of natural products drug discovery, only we generally haveto stop at the lead in most cases. But, often times, depending upon what thegoal is, the lead may in fact be good enough. I would also hope that mostunderstand that even the slightest change in a molecule can yield substantiallydivergent pharmacokinetic and pharmacodynamic properties.

In any case, this brings us to the next point which is that there is more toconsider aside from bioavailability and half-life. If a particular compoundpossesses the necessary potency at whatever your given molecular target may be,the bioavailability in particular may not be of much importance, especially ifthere is room for a variable dose. For example, if the concentration needed foractivity is in the picomolar or nanomolar range and the given compound yieldsserum concentrations in that range after administration of 1,000 mg or 3,000mg, what does it matter if the bioavailability is only 5%? The answer is thatit doesn't.

I think discussion is great and reviews like this are a great way to sparkexperimentation and improve study design, but let's be better than simplytaking a hypothesis and using it as a justification to say whether somethinghas value or not. In fact, if we want to respect science at all, let's not takehypotheses and use them as, "facts", which in reality, do not existto begin with.

Very good info. Good points.

 

[rome32]

Very good info. Good points.

Agreed. Best post I've read.

 

[mr.cooper69]

Thank you USPlabs/lead formulator for the response. I will mull over it for a bit and PM you with my thoughts. This is exactly the kind of response that can build discussion on the topic

 

[JudoJosh]

:grouphug:

 

[Whacked]

THIS
Good stuff USP

Thank you USPlabs/lead formulator for the response. I will mull over it for a bit and PM you with my thoughts. This is exactly the kind of response that can build discussion on the topic

 

[DCbuilder]

Thank you USPlabs/lead formulator for the response. I will mull over it for a bit and PM you with my thoughts. This is exactly the kind of response that can build discussion on the topic

I respect you a lot mr c, and u do what u want, but this is not helpful for the "discussion" here int he community. Why PM him when you can further the discussion right here? Especially after attacking the product w/ a response in this thread? He posts info so we can read, why can't we hear your "counterpoint"?

Instead, it appears, we won't know what you think about the product in return, and now we are left w/ no closure on the issue. Kind of sucks. Truly.

 

[FL3X MAGNUM]

I respect you a lot mr c, and u do what u want, but this is not helpful for the "discussion" here int he community. Why PM him when you can further the discussion right here? Especially after attacking the product w/ a response in this thread? He posts info so we can read, why can't we hear your "counterpoint"?

Instead, it appears, we won't know what you think about the product in return, and now we are left w/ no closure on the issue. Kind of sucks. Truly.

Find me one brainiac that doesn't enjoy some advanced discussion. Coop was not attacking. He was stating his opinion. It was pointed out that it came across as aggressive, therefore he stated he would PM all further points of discussion out of respect to USP.

Why does everyone love drama so much? You guys are feeding off of negativity. Enough already.

 

[FL3X MAGNUM]

Furthermore, this isnt bb.com.
Our opinions are actually welcome here.
I like USP, so I have no negative arguments towards them on this issue.

 

[freezito]

Some people just love to hate. U can say usplabs isn't professional that's your opinion but there isn't a company who's given more then they have.

 

[ax1]

I respect you a lot mr c, and u do what u want, but this is not helpful for the "discussion" here int he community. Why PM him when you can further the discussion right here? Especially after attacking the product w/ a response in this thread? He posts info so we can read, why can't we hear your "counterpoint"?

Instead, it appears, we won't know what you think about the product in return, and now we are left w/ no closure on the issue. Kind of sucks. Truly.

Problem is that sometimes reps are in position of losing their jobs if they get banned. This board is much freer than the other popular board but you never know if complaints from company owners come in.

 

[DCbuilder]

Problem is that sometimes reps are in position of losing their jobs if they get banned. This board is much freer than the other popular board but you never know if complaints from company owners come in.

This is what I don't get...

why would anyone in this thread (such as mr. c) get banned?

This thread is full of people taking things far too extreme. It's simple:

We have a product
Some question how or why it works, and thinks it won't
Company responds

Let's forget the drama and nonsense and continue the discussion. No one should be scared or think they'll get banned or go insane. Just talk. Thanks.

 

[freezito]

Find me one brainiac that doesn't enjoy some advanced discussion. Coop was not attacking. He was stating his opinion. It was pointed out that it came across as aggressive, therefore he stated he would PM all further points of discussion out of respect to USP.

Why does everyone love drama so much? You guys are feeding off of negativity. Enough already.

Life is drama

 

[ax1]

This is what I don't get...

why would anyone in this thread (such as mr. c) get banned?

This thread is full of people taking things far too extreme. It's simple:

We have a product
Some question how or why it works, and thinks it won't
Company responds

Let's forget the drama and nonsense and continue the discussion. No one should be scared or think they'll get banned or go insane. Just talk. Thanks.

Its politics. Work behind the scenes long enough you understand whats going on a little better.

 

[madchemist]

Since I'm an adrenergic pharmacology guy, I'll keep my discussion confined to the two phenylpropenic acid derivatives which are purported to be present in "Compound 20."

Unfortunately for USPLabs, neither of these compounds are novel, and neither exist in a pharmacological vacuum - both of their structure activity relationships have been explored for at least the last 5 decades. From an in vitro petri dish, to actual human pharmacokinetic models, we know with a high degree of certainty the metabolic pathways that these compounds will follow. Furthermore, the pharmaceutical industry has spent untold billions to develop drugs to bypass these pathways to increase a drugs effiaciousness and potency.

Speaking of N-Coumaroyldopamine (which has the most potential of the two), we know that it will be highly susceptible to both 1) methylation at the benzene hydroxyl groups and 2) amide hydrolysis (in addition to phase II metabolism). Both events take place in the gastric lumen, in addition to the liver, and so the amount of intact drug reaching systemic circulation probably hovers around 0-1%. After amide hydrolysis, we are left with dopamine + an inert metabolite. Dopamine has almost zero CNS penetration, and its half-life is about 2 minutes. Ultimately, both N-coumaroyldopamine and its metabolites will be completely eliminated within 3-5 minutes. A COMT inhibitor probably will be of no value, since it is physiologically impossible to inhibit amide hydrolysis (which is why pharmaceutical derviatives are amines, not amides).

 

[madchemist]

Ultimately, the only way for either of these compounds to work en vivo as they did en vitro (i.e. beta2 agonism), is to inhibit every phase of human metabolism (which is obviously not possible), in addition to altering the pH of the gastric lumen in order to limit amide hydrolysis (possible).

If you wanted to build a better stimulant based off the n-coumaroyldopamine skeleton, make a bioisostere, substituting the benzene -OH's for chlorides, and change the amide for an amine. An alpha methyl wouldn't hurt.

 

[Whacked]

No clue who this mad chemist is but he sure sounds smart

Will someone dumb it down for the rest of us?

The translation I got was that the ingredients in C-20 won't work or could but need to be altered?

 

[USPlabsRep]

Ultimately, the only way for either of these compounds to work en vivo as they did en vitro (i.e. beta2 agonism), is to inhibit every phase of human metabolism (which is obviously not possible), in addition to altering the pH of the gastric lumen in order to limit amide hydrolysis (possible).

If you wanted to build a better stimulant based off the n-coumaroyldopamine skeleton, make a bioisostere, substituting the benzene -OH's for chlorides, and change the amide for an amine. An alpha methyl wouldn't hurt.

OUr last response, We have more pressing issues...

I thought I had covered this rather thoroughly but apparently not. You areimplying that using SAR, you can predict not only all pathways, but moreimpressively or actually downright astonishingly, you can predict the oralbioavailability of a compound without it ever being studied, down to a marginof error of 1% apparently with your 0-1% prediction and complete eliminationfrom the body in 3-5 minutes. I have worked in drug discovery and I must say,your ability to do what no one else in history can do places you in an unrealcategory. Pharmaceutical companies would pay you millions atop of millions tobe able to do this. Your accuracy of 99% would put all in silico models toshame. Software developers will be beating down your door with millions andmillions. And who needs animal models any more, they''ll just have you predicteverything.

And despite your generalization that the pharmaceutical industry has investedbillions to bypass various metabolic pathways, you are neglecting other reasonswhy various derivatives are made and two major factors come down to being costefficient and intellectual property. A compound with good activity that isnaturally occurring is still worthless because it can not be patented as aninvention. Second, when you are talking about the cost of production, it alwaysmakes more sense to have a compound which can be used in microgram and lowmilligram quantities, hence a major reason for taking something with 5-10%bioavailability and attempting to get it into the 90% or better range. Itdecreases costs from every aspect of production from synthesis tomanufacturing, transport, etc. This is why a naturally occurring compound with5% bioavailability wouldn't be preferred by a pharmaceutical company, notbecause it is worthless as you imply (and of course as I said, there are stillsome pharmaceuticals used today with very low bioavailability). Potency factorsin here as well. Of course, there are also more legitimate reasons whyderivatives are made as well (e.g., improving selectivity, decreasing toxicity,improving stability, solubility, etc.) but you are again making a broad andincorrect generalization.

It's unfortunate because you are bringing up valid points and these are likelyroutes of metabolism, but to pretend as if you know to what extent and to goeven further and predict exact bioavailability is just absurd and not possible.That is not pharmacology and not science and there is no pharmacologist orscientist that would ever make such claims.

To correct a few of your statements that you seem so certain about. Acid-labiledrugs are still employed all the time so I'm not sure what you're talkingabout. Enteric coatings, formulation with a buffer and pro-drugs have all beenused. Further, despite what you say, there are many amides used inpharmaceuticals.

Regarding your comment about, "building a better version", you couldalso move the hydroxyl from the 4 position to the 5 (which also confers COMTresistance as with all resorcinols) or you could then take both, move thehydroxyl from the 4 to the 5 and replace with Cl and put an amine at the 4position and you'd have clenbuterol which is resistant to COMT and first passconjugation (PST) while having better lipophilicity, as is the otherhalogenated haloaniline, mabuterol. Or, you could replace the hydroxyl group atthe 3 position with a hydroxymethyl and you'd have the saligenins likesalbutamol and salmeterol. And don't forget to have a large N-alkyl substituentto increase selectivity away from alpha-adrencoceptor toward the beta2-adrenoceptor. But, this doesn't need to be done at all with the entire seriesof catechol beta 2-adrenoceptor agonists. According to you, these are worthlesssince they are substrates for COMT and PST, yet bioavailability studies sayotherwise. What is your point exactly anyway? These are natural products, notpharmaceuticals; such changes create a drug, not a dietary supplement.

If you really want to continue pushing this notion, why don't we do this. Howabout we complete 3 bioavailability analyses on 3 compounds which have nopublished studies evaluating such. Then, we can present these compounds to youand you can predict the bioavailabilty. Even though you apparently have theability to predict within 1%, I'll give you a 5% margin of error for yourprediction on each compound. If you predict them correctly, you'll have a$1,000 check waiting for you and I will introduce you to 2 large drug discoverylabs that I still have connections with. If you can't, you'll have to stop thissilliness about predicting pharmacokinetic parameters by simply taking a lookat two similar looking molecules and making generalizations. Instead, you'llhave to rely upon the scientific method which involves experimental results toevaluate the validity of your proposed hypothesis.