Talk:Picamilon

Structural Inaccuracy

The picture is of the sodium salt form (Pubchem: 3047131), not the acid form (Pubchem: 60608). It should be changed. Fuzzform 02:54, 12 February 2007 (UTC)

Will update with an SVG (Ccroberts^{( t · c · g )} 05:31, 9 July 2007 (UTC))

Updated with high-res png. took a little longer than expected ;p (Ccroberts^{( t · c · g )} 14:27, 16 August 2007 (UTC))

GHB Analogue?

Does anyone know of the existence of a GHB/Niacin analogue to this substance? Just curious. (Ccroberts^{( t · c · g )} 05:31, 9 July 2007 (UTC))

Don't know but this isn't it. —Preceding unsigned comment added by 71.107.230.145 (talk) 20:09, 21 February 2008 (UTC)

I'd like to underline that Picamilon is almost NOT metabolized in humans to GABA and niacin but is eliminated unchanged. Please correct this one. — Preceding unsigned comment added by Hyperwind (talk • contribs) 10:10, 13 March 2011 (UTC)

That may very well be, but either way, we need reliable source to document that picamilon is or is not a prodrug of GABA and niacin. Apparently a large fraction of picamilon is excreted unchanged, but what is the fate of the rest of the ingested picamilon? Many of the cited sources in this article are written in Russian and I notice that you are Russian. Do any of these source shed more light on the pharmacokinetic/metabolic fate of picamilon? Boghog (talk) 12:59, 13 March 2011 (UTC)

Actually, they do. All the sources on pharmacokinetics of Picamilon state that "it is eliminated unchanged, mostly via kidneys" which is different from saying that "it is mostly eliminated unchanged via kidneys". Morover, its annotation, issued by the manufacturer(s), state the same. Even more, the Russian researchers of the drug emphasize that the action of Picamilon involves mechanisms different from GABA and niacin as it is "not metabolized into niacin and GABA in human tissues but excreted unchanged with urine... which makes us think that it involves totally another mechanism of action that we are to reveal further" [Picamilon in modern neurological and Psychiatric practice /Erokhina L.G., Stakhovskaya L.V., Chekneva N.S. and others // Materials of Russian conference Moscow, 1994. — pages 71–74.]

More to that, Russian branch of Vidal states that "Picamilon is retained for a long period of time by human tissues. it is excreted mostly by kindeys, unchanged". http://www.vidal.ru/poisk_preparatov/picamilon__9005.htm http://www.vidal.ru/poisk_preparatov/act_1741.htm

comment added by Hyperwind

Thanks for checking the Russian citations. However citation #4 provides strong evidence that Picamilon is a pro-drug. In this paper, IP injection of Picamilon (referred to as isonicotinoyl-γ-aminobutryic acid or IG in the paper) caused a statistically significant increase in concentration of GABA in the brain. Furthermore the increase in GABA caused by IG and an analog of IG, NG correlated with their respective in vivo potencies. Concerning the metabolism, the critical question is "what percent of administered drug is recovered unchanged?" which is not answered by stating "no metabolites were detected, only unchanged parent drug was found in the urine ". Total recovery is very difficult to quantitate unless radio-labeled drug is used. Furthermore, the hydrolysis products of Picamilon, GABA and niacin, would be very difficult to detect given the high background levels of both compounds that are normally found within humans (unless again Picamilon were radio-labeled). Even if close to 100% of the drug is excreted unchanged in the urine, this does not rule out the possibility that a small fraction could be hydrolyzed in the brain and the hydrolyzed metabolites are responsible for its activity. Boghog (talk) 10:45, 4 December 2011 (UTC)

Many drugs influence concentrations of different chemicals in tissues not being their precursors. It's pharmacology 101 :) MAO inhibitors raise, for example, serotonin (& catecholamines) levels in brain tissues not being precursors to serotonin (& catecholamines) themselves (but by blocking MAO enzyme that breaks them down). Many drugs are intended to stimulate synthesis of different chemicals from their respective precursors deposited in tissues. The clinical and lab studies I've read all point to a mediated GABAergic action of Picamilon which is the reason for GABA concentration in the brain going up rather than to Picamilon being a GABA precursor. Besides, if it was, it would raise a question: WHY larger amount of Picamilon isn't metabolized? Hyperwind Hyperwind (talk) 16:32, 4 December 2011 (UTC)

I agree that Picamilon may indirectly raise the concentration of GABA in the brain either by stimulating its synthesis or release from synapses, or by inhibiting its degradation or re-uptake. But is there any direct evidence that Picamilon works through this mechanism? The short answer to why Picamilon isn't metabolized to a greater extent is that it is a stable amide that is only very slowly hydrolyzed and there are no enzymes that can efficiently hydrolyze it. Slow hydrolysis could explain both the modest increases in GABA in the brain and why the majority of Picamilon is excreted unchanged in the urine. Hence we are back where we have started. There is no direct evidence to prove or disprove that Picamilon acts as a pro-drug. Finally a more important question of whether Picamilon has any pharmacological effect to begin with. Are there any controlled clinical studies proving Picamilon's efficacy? If there is no efficacy, the question of whether Picamilon acts as a pro-drug becomes moot. Boghog (talk) 19:50, 4 December 2011 (UTC)

It is a renowned, powerful and balanced (doesn't lead to 'robbing phenomenon') cerebral vasodilator, which is proven by many studies. That is the only effect reliably proven till now, but many researchers emphasize the fact that, according to their study, Picamilon enlarges the blood vessels by itself, it doesn't involve niacin. It's really a VERY cheap drug (in Russia) - 30x 50mg pills per bottle is only 2$, it's manufactured by several competing companies, so there's no reason for anybody to promote Picamilon, if you suspect this)))--Hyperwind (talk) 17:12, 5 December 2011 (UTC)

Elimination Half-Life

I added some data about Picamilon's elimination half-life that I found on the drug's leaflet.

What the leaflet says exactly is "0.51 hours", which I assumed to be around 30 minutes. Not sure if that is correct (might be 51 minutes).

Lysergsaure 10:07, 1 August 2007 (UTC)

That seems like about the right amount of time, as the molecule would be cleaved into gaba and niacin pretty quickly. I can't seem to find the data anywhere, quickly anyway. (Ccroberts^{( t · c · g )} 14:27, 16 August 2007 (UTC))

Asthenia Link

There was a wiki link from the word "asthenic" that pointed to Dependent Personality Disorder. I have changed it to point to Asthenia. I'm assuming it was incorrectly pointing to Dependent personality disorder. If I am mistaken, please undo.

APatcher (talk) 03:47, 29 May 2008 (UTC)

Quackery?

There seems to be little support in the published literature for most of the claims in the current previous clinical studies section of this article. A quick Google search reveals that picamilon is being sold as a food supplement with claims similar to the ones contained in this article, but again with no verifiable sources to back up these claims. Finally this article has included a Refimprove banner since September 2007 and with the exception of a few citations that I have added, no one has responded to. Hence I am rapidly coming to the conclusion that picamilon is an experimental drug with a plausible mechanism of action which has failed to show any clinical benefit. Unless someone steps foward with reliable sources to support the claims being made about picamilon, I propose to remove the clinical studies section of this article. Boghog2 (talk) 05:25, 31 May 2008 (UTC)

Copyright violation

Much of the material contained in this article appears to have been copied verbatim from:

• R.P. Kruglikova (July 1997). "How And Why Picamilon Works". Life Extension Magazine. Retrieved 2008-05-28. All Contents Copyright © 1995-2008 Life Extension Foundation All rights reserved. {{cite web}}: Cite has empty unknown parameter: |coauthors= (help)

Therefore In addition to the verifiability issue mentioned above, there is also a copyright violation. Boghog2 (talk) 09:30, 31 May 2008 (UTC)

Explanation for deletion

Because of the WP:COPYVIO and WP:RELIABLE issues mentioned above, I have deleted the clinical studies section of this article. Boghog2 (talk) 09:57, 31 May 2008 (UTC)

Origin

It is known for a long time in Nutropics user community that Picamilon originated in Russia since 1969. The first scientific paper in the West doesn't mean the authors are the inventors of this medicine. Please google "Picamilon 1969" or "site:www.springerlink.com Picamilon 1969" to see some interesting result. —Preceding unsigned comment added by 124.121.207.32 (talk) 07:18, 25 June 2008 (UTC)

Thanks for correcting this. My mistake. Cheers. Boghog2 (talk) 08:35, 25 June 2008 (UTC)

GABA Analogue

Nowhere in the article is picamilon identified as a GABA analogue, but it is listed in the category of GABA analogues. Is it an analogue? If so, it should be cited in the article. If not, the category should be removed, IMO. cheers. anastrophe, an editor he is. 01:51, 6 October 2023 (UTC)

The lead sentence states drug formed by a synthetic combination of niacin and γ-aminobutyric acid (GABA). A structural analog is a compound having a structure similar to that of another compound. Hence by definition, picamilon is both a GABA analog and a niacin analog. Boghog (talk) 04:17, 6 October 2023 (UTC)

Fair enough, but I'm an 'average reader' of the encyclopedia here - I don't know any of this stuff. The reason it's problematic is because of how I got to this article - I had visited the GABA article; towards the end of the article it has a section on 'GABAergic drugs'; below the table, it lists 'Other GABAergic modulators'; there are three cite requests dating to 2016 in that list; curious, I opened each article for the 'GABA analogues' that were listed, to see why that list was cite req'd; of the four listed, only picamilon didn't overtly state that it's a GABA analogue. That's the twisted path of the editor who likes to either cite or cull cite req'd material. :) cheers. anastrophe, an editor he is. 05:35, 6 October 2023 (UTC)