Phenibut Information

I haven't seen any discussion of this compound here. Here is an article I wrote on it.


Introduction

Phenibut (beta-phenyl- gamma-aminobutyric acid, also spelled fenibut, originally known as phenigamma) is a derivative of the neurotransmitter GABA that crosses the blood-brain barrier [1]. It was developed in Russia, and there it has been used clinically since the 1960's for a range of purposes. Phenibut has both nootropic and anxiolytic (anxiety-reducing) properties, and it is commonly compared to diazepam (Valium), baclofen, and piracetam, and it has similarities to and differences from all of these substances.

Structurally, phenibut is similar to GABA, baclofen (p-Cl-phenibut), and beta-phenylethylamine (PEA). GABA is the primary inhibitory neurotransmitter in the brain. The addition of the phenyl ring to GABA allows the compound to more easily cross the blood-brain barrier, but also changes its activity profile [1-2]. Baclofen is a drug commonly used in studies on GABA(B) receptors, and also clinically used to treat severe spasticity of cerebral origin [3]. PEA is a naturally occuring biogenic amine which is similar in structure to amphetamine, and like amphetamine, it is a stimulant that causes the release of dopamine, and also promotes anxiety in high enough amounts.

Phenibut is a GABA receptor agonist and also causes the release of GABA. Similar to baclofen, phenibut is an agonist at GABA(B) receptors, although it does have some effect on GABA(A) receptors as well [2]. It is possible that phenibut has a higher activity at central GABA(B) receptors than peripheral ones [4]. The role of the GABA(B) receptor is not well-established, although research in the last seven years has significantly increased our understanding of this receptor. The most well-established role of GABA(B) receptors is inhibition of the release of some neurotransmitters, and it may also serve as a negative feedback mechanism for GABA release [5-6].

Because of the structural similarity to PEA, phenibut may share some similarities and differences with it. When phenibut is administered along with PEA, it antagonizes many of its effects, such as promotion of anxiety, promotion of seizures, and hyperthermia. This has lead some to postulate that antagonism of PEA, rather than the GABA-mimetic activity, may be the important mechanism of action for tha anxiolytic effect of phenibut [2, 7]. Phenibut also increases dopamine levels, and it has been postulated that the structural similarity to PEA may play a role in this effect [2].

There is one report in the literature of serotonergic effects of phenibut [8], but it does not look as though this has been followed up on.

Effects of phenibut

Anxiety reduction. Phenibut is effective in many animal models of anxiety, although there is often dependence on study conditions. In cats classified as "anxious" or "passive," phenibut reduced the fear response and increased aggression in a confrontational situation, while it had no effect on aggressive cats. In normal cats, it lead to "positive emotional symptoms" [2]. In mice, phenibut increased social behavior [9]. In rats, phenibut decreased some of the physiological responses to stress, including the elevation of glucocorticoid levels [10]. Phenibut has also been reported to decrease the fear response caused by electrical stimulation and counteract the anxiogenic effect of the beta-carboline DMCM [2, 11]. Studies in rats examined the behavioral properties of phenibut when it was administered locally into different parts of the brain, and it usually lead to a reduction of anxiety in one or more models [12-16].

The results of animal models don't always pan out in the real world, however, phenibut has a mechanism of action similar to that of many drugs which are known to reduce anxiety in humans. Animal studies have compared the profile of phenibut to diazepam (Valium), which has pronounced anxiolytic properties, and piracetam, which has weak anxiolytic properties. One study found phenibut had a tranquilizing effect similar to, but weaker than diazepam. It also caused sedation and muscle relaxation (whereas piracetam did not), but again these effects were weaker than those caused by diazepam [2].

In Russia, phenibut is commonly used to treat many neuroses, including post-traumic stress disorder, stuttering, and insomnia. In double blind placebo-controlled studies, phenibut has reportedly been found to improve intellectual function, improve physical strength, and reduce fatigue in neurotic and psychotic patients [2].

Nootropic effects. Although phenibut does not meet all the requirements of a nootropic, it does have many similarities to piracetam. In mice, phenibut causes significant improvement on the passive avoidance test [2]. In this test of memory, animals are put in an undesirable area (such as a lighting situation or height from the floor that that species dislikes), and then given a negative stimulus (such as a shock) when they exit that area. Their ability to stay in the original area reflects how well they remember that if they exit it, they will receive the undesirable stimulus. Phenibut also improves performance on the swimming and rotarod tests and antagonizes the amnestic effect of chloramphenicol [2]. It also has an antihypoxic effect, a trait commonly seen among nootropics [17]. However, in one study, phenibut was ineffective in the water maze and shuttle box tests, while piracetam was [18]. Other research supports the idea that phenibut has nootropic activity similar to that of piracetam, but not as strong [19]. Nootropic activity has also been reported in humans [2], but it was not specified whether these were healthy adult humans, and they were probably elderly or psychiatric patients.

Another trait phenibut shares with nootropics is neuroprotection. Multiple animal studies have indicated that phenibut administration increases resistance to the detrimental effects of edema on mitochondria and energy production in the brain [20-22]. Phenibut also normalizes brain energy metabolism changes caused by chronic stress [23]. It was found to prevent changes in plasma electrolytes caused by cerebral injury [24]. Phenibut also protects dopaminergic neurons, and improved the condition of patients being treated with antiparkinsonic drugs [25].

Other effects. Phenibut has anticonvulsant activity against some drugs or conditions, but not others. It also potentiates the action of some other anticonvulsant drugs, and has been used to treat patients with epilepsy [2]. Phenibut has been reported to reduce motion sickness, and used in the treatment of alcohol and morphine withdrawal [2, 26]. One study indicated that phenibut increased resistance to heat stress and improved working capacity in humans [27].

Some studies indicate that phenibut has anti-arrhythmic properties in humans [28-29]. It also has other cardioprotective properties [30-31]. Finally, phenibut showed promise in experimental models of gastric lesions [32-33].

Side effects and suggested use

Phenibut has low acute toxicity. Reported LD50s (dose required to kill 50% of laboratory animals) are 900 mg/kg i.p. in mice, 700 mg/kg i.p. in rats, and 1000 mg/kg in rats (method of administration not given) [2, 34]. Chronic administration of 50 mg/kg did not have teratogenic effects in rats [34]. In clinical studies, no signs of toxicity have been reported, and side effects are few. Some report drowsiness, but this effect is not nearly as likely or severe as with benzodiazepines [2].

One should be aware of the potential for drug interactions when taking phenibut. In many cases, it will decrease the threshold dose and potentiate certain actions of a drug. It amplifies some of the effects of anesthetics (ether, chloral hydrate, and barbiturates), diazepam, alcohol, and morphine [2, 35-36]; it would also presumably have an interaction with related drugs, such as other opiates and GHB. In contrast, taking phenibut with some other drugs, such as stimulants, will more than likely just blunt their effect.

In humans, the plasma half-life after a 250 mg oral dose of phenibut is 5.3 hours, and most of the administered drug is excreted unchanged [2]. Reported dosages used in clinical studies range from 250 to 1500 mg daily, usually divided among three doses [2, 37]. Feedback indicates that the ideal dose may be in the higher end of this range.

Tolerance develops to many of the effects of phenibut, although it is reported that it does not develop to the nootropic effect. The first signs of tolerance may be seen within as little as five days. For this reason, it is commonly used for one to two week periods, or dosage is increased by 25-30% after two weeks [2]. This makes phenibut ideal for short periods of stress or anxiety, but not ideal for chronic use. It is possible that taking only one dose daily may partially reduce the development of tolerance.

If you have any questions or comments regarding this article, please email dvdtlsn@bulknutrition.com.

No part of this article may be reproduced in any form without the permission of David Tolson or Mike McCandless.

References

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2. Pavlov J Biol Sci. 1986 Oct-Dec;21(4):129-40. On neurotransmitter mechanisms of reinforcement and internal inhibition. Shulgina GI.

3. Curr Drug Target CNS Neurol Disord. 2003 Aug;2(4):248-59. GABA(B) receptors as potential therapeutic targets. Vacher CM, Bettler B.

4. Eur J Pharmacol. 1993 Mar 16;233(1):169-72. R-(-)-beta-phenyl-GABA is a full agonist at GABAB receptors in brain slices but a partial agonist in the ileum. Ong J, Kerr DI, Doolette DJ, Duke RK, Mewett KN, Allen RD, Johnston GA.

5. Am J Physiol Gastrointest Liver Physiol. 2001 Aug;281(2):G311-5. Receptors and transmission in the brain-gut axis: potential for novel therapies. IV. GABA(B) receptors in the brain-gastroesophageal axis. Blackshaw LA.

6. Prog Neurobiol. 1995 Jul;46(4):423-62. A physiological role for GABAB receptors and the effects of baclofen in the mammalian central nervous system. Misgeld U, Bijak M, Jarolimek W.

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9. Pharmacol Biochem Behav. 1981;14 Suppl 1:53-9. Pharmaco-ethological analysis of social behaviour of isolated mice. Poshivalov VP.

10. Biull Eksp Biol Med. 1987 Nov;104(11):588-90. [Role of the GABAergic system in the mechanism of the stress-regulating action of phenibut] [Article in Russian]. Kovalev GV, Spasov AA, Bogachev NA, Petrianik VD, Ostrovskii OV.

11. Pharmacol Toxicol. 1990 Jan;66(1):41-4. Stress-protection action of beta-phenyl(GABA): involvement of central and peripheral type benzodiazepine binding sites. Rago L, Kiivet RA, Adojaan A, Harro J, Allikmets L.

12. Neurosci Behav Physiol. 2003 Mar;33(3):255-61. Neurochemical characteristics of the ventromedial hypothalamus in mediating the antiaversive effects of anxiolytics in different models of anxiety. Talalaenko AN, Pankrat'ev DV, Goncharenko NV.

13. Eksp Klin Farmakol. 2002 Sep-Oct;65(5):22-6. [Monoaminergic and aminoacidergic mechanisms of the posterior hypothalamus in realization of the antiaversive effects of anxiosedative and anxioselective agents in various anxiety models] [Article in Russian]. Talalaenko AN, Pankrat'ev DV, Goncharenko NV.

14. Ross Fiziol Zh Im I M Sechenova. 2001 Sep;87(9):1217-26. [Neurochemical characteristics of the ventromedial hypothalamus and anti-aversive effects of anxiolytic agents in various anxiety models] [Article in Russian]. Talalaenko AN, Pankrat'ev DV, Goncharenko NV.

15. Eksp Klin Farmakol. 2000 Jan-Feb;63(1):14-8. [The neurochemical profile of the caudate nucleus in the anxiolytic action of benzodiazepine and nonbenzodiazepine tranquilizers on different models of anxiety] [Article in Russian]. Talalaenko AN, Gordienko DV, Markova OP.

16. Ross Fiziol Zh Im I M Sechenova. 1997 Mar;83(3):88-94. [Neurochemical analysis of the amygdala basolateral nucleus of rats during anxiety tests] [Article in Russian] Talalaenko AN, Babii IuV, Perch NN, Vozdvigin SA, Panfilov VIu.

17. Biull Eksp Biol Med. 1984 Feb;97(2):170-2. [Nootropic properties of gamma-aminobutyric acid derivatives] [Article in Russian]. Ostrovskaia RU, Trofimov SS.

18. Farmakol Toksikol. 1984 Jan-Feb;47(1):20-3. [Comparative characteristics of the nootropic action of fenibut and fepiron] [Article in Russian]. Kovaleva EL.

19. Farmakol Toksikol. 1987 Jul-Aug;50(4):18-22. [Normalizing effect of GABA derivatives on late behavioral disorders occurring in rats with early postnatal suppression of protein synthesis] [Article in Russian]. Burov IuV, Ostrovskaia RU, Smol'nikova NM, Trofimov SS, Savchenko NM.

20. Eksp Klin Farmakol. 1994 Mar-Apr;57(2):13-6. [The effect of fenibut on the ultrastructure of the brain mitochondria in traumatic edema and swelling] [Article in Russian]. Novikov VE, Naperstnikov VV.

21. Farmakol Toksikol. 1991 Nov-Dec;54(6):44-6. [The effect of GABA-ergic agents on oxidative phosphorylation in the brain mitochondria in traumatic edema] [Article in Russian]. Novikov VE, Sharov A.

22. Farmakol Toksikol. 1984 May-Jun;47(3):35-8. [Effect of benzodiazepine and GABA derivatives on the energy metabolism indices in brain edema] [Article in Russian]. Novikov VE, Kozlov SN, Iasnetsov VS.

23. Ukr Biokhim Zh. 1984 Nov-Dec;56(6):637-41. [Mg2+-ATPase activity of brain mitochondria fractions in chronic stress and its correction by psychotropic agents] [Article in Russian]. Kresiun VI.

24. Eksp Klin Farmakol. 1992 May-Jun;55(3):70-2. [The effect of GABA-ergic agents on the blood electrolyte balance in acute craniocerebral trauma] [Article in Russian]. Novikov VE, Chemodurova LN.

25. Zh Nevropatol Psikhiatr Im S S Korsakova. 1986;86(8):1146-8. [Phenibut potentiation of the therapeutic action of antiparkinson agents] [Article in Russian]. Gol'dblat IuV, Lapin IP.

26. Farmakol Toksikol. 1991 Sep-Oct;54(5):14-6. [The adequacy of a new method for assessing the vestibular protective effect of biologically active substances] [Article in Russian]. Karkishchenko NN, Dimitriadi NA.

27. Eksp Klin Farmakol. 1997 Jan-Feb;60(1):68-71. [The enhancement of human thermal resistance by the single use of bemitil and fenibut] [Article in Russian]. Makarov VI, Tiurenkov IN, Klauchek SV, Nalivaiko IIu, Antipova AIu.

28. Kardiologiia. 1987 May;27(5):48-52. [Differential psychopharmacotherapy of heart rhythm disorders] [Article in Russian]. Skibitskii VV.

29. Ter Arkh. 1986;58(11):97-101. [Clinico-hemodynamic effects of psychotropic preparations and psychosomatic correlations in cardiac rhythm disorders] [Article in Russian]. Petrova TR, Skibitskii VV.

30. Farmakol Toksikol. 1983 May-Jun;46(3):41-4. [Effect of tranquilizers on myocardial function in stress injury] [Article in Russian]. Kovalev GV, Gurbanov KG, Tiurenkov IN.

31. Farmakol Toksikol. 1983 Jan-Feb;46(1):38-41. [Effect of tranquilizers on the course of myocardial ischemia and on myocardial resistance to hypoxia in coronary artery occlusion] [Article in Russian]. Kovalev GV, Gurbanov KG, Tiurenkov IN, Naidenov SI.

32. Patol Fiziol Eksp Ter. 1995 Jan-Mar;(1):21-3. [Central mechanisms of neurogenic gastric lesion and its pharmacologic correction] [Article in Russian]. Bul'on VV.

33. Biull Eksp Biol Med. 1990 Nov;110(11):504-6. [The effect of GABA-ergic agents on the development of a neurogenic stomach lesion in rats] [Article in Russian]. Bul'on VV, Zavodskaia IS, Khnychenko LK.

34. Farmakol Toksikol. 1989 Jul-Aug;52(4):37-9. [Effect of fenibut and seduxen on fetal development in the second half of pregnancy] [Article in Russian]. Filimonov VG, Sheveleva GA, Strel'chenko NV, Sizov PI, Iasnetsov VS.

35. Biull Eksp Biol Med. 1985 Jun;99(6):698-700. [Effect of fenibut on the GABA B receptors of the spinal motor neurons] [Article in Russian]. Abramets II, Komissarov IV.

36. Arch Immunol Ther Exp (Warsz). 1975;23(6):733-46. Pharmacological properties of gamma-animobutyric acid and it derivatives. IV. Aryl gaba derivatives and their respective lactams. Chojnacka-Wojcik E, Hano J, Sieroslawska J, Sypniewska M.

37. Med Tr Prom Ekol. 1997;(5):35-8. [Experimental bases of the use of pharmacologic agents aimed at higher heat resistance of humans as means of individual protection] [Article in Russian]. Makarov VI, Tiurenkov IN, Klauchek SV, Nalivaiko IO, Antipova AIu.

Article from: http://www.bulknutri...gredients_id=64

I've recently had a chance to use Phenibut with great results as a mood elevating & relaxing compound, but I did not notice any immediate cognitive enhancement. When I have a chance I’ll try it for a month straight and see what happens.

Click HERE to rent this advertising spot for SUPPLEMENTS (in thread) to support LongeCity (this will replace the google ad above).

Yeah, I consider piracetam to be among the weaker nootropics, and phenibut is even weaker, but most anxiolytics, at least stronger ones, have a mind-dulling effect, so even not having this effect is an advantage. For someone prone to anxiety, phenibut is probably more likely to increase clarity of thought, etc.

Piracetam one of the weaker Nootropics??

I'm assuming this is your personal experience, which is fine as some people don't "feel" the effects of Piracetam.

But in terms of the # effects in the brain it is one of the strongest or best nootropics to take. Also being the most and one of the longest studied nootropics compared to newer forms such as Aniracetam or Pramiracetam, in which the dosage used is less but this effect has been studied mostly in animals and in regards to only some of the cognitive effects of Piracetam, not all the known effects of piracetam.


Phenibut I would not consider a nootropic (see Nootropic's Q/A for more on that), but I'm sure it does help if stress is impacting your memory.

Is Phenibut much different than Picamilon??

Is Phenibut much different than Picamilon??

I have not tried phenibut, but picamilon does have some calming effects, not sedative, at low doses (50mg/2 times a day). Some have complained of a pro-anxiety effect after using picamilon for several weeks, but I don't know what doses they were using. Picamilon and Phenibut are structurally related, in being GABA derivatives (phenibut = beta-phenyl-GABA, picamilon = nicotinoyl-GABA). Picamilon was shown to be more potent cerebral dialator than vinpocetine and more effective in the radial maze test than piracetam.

Would Picamilon be a better alternative to Vinpocetine? What about someone with slightly high blood pressure? I was thinking that I should avoid too potent a vassilador, as per my doctor's recommendation, would their be any danger in me taking Picamilion over Vinpocetine? Obviously the Vinpo is on it's way so I can't change that and I'm relatively comfortable with using it, but if Picamilion offers a clear advantage than I might use it over Vinpo.

Phenibut is far stronger as a relaxing drug than Picamilon, but Picamilon appears to be the best for increasing CBF.


Vinpocetine (and more so Vincamine) can lower blood pressure, but I have not seen any studies suggesting Picamilon would raise it.

I personally recommend Vincamine over Vinpocetine because its more potent and unlike Vinpocetine it is effective in AD.

I'll look into Vincamine and Picamilon further, from your information it seems like Vinpo is safe for me even with my slightly high blood pressure. I'll stick with Vinpo right now, but I'll add Vincamine and Picamilon to the list of vassiladors that I might research and dabble with at some point in the future.

Piracetam one of the weaker Nootropics??

I'm assuming this is your personal experience, which is fine as some people don't "feel" the effects of Piracetam.

But in terms of the # effects in the brain it is one of the strongest or best nootropics to take. Also being the most and one of the longest studied nootropics compared to newer forms such as Aniracetam or Pramiracetam, in which the dosage used is less but this effect has been studied mostly in animals and in regards to only some of the cognitive effects of Piracetam, not all the known effects of piracetam.


Phenibut I would not consider a nootropic (see Nootropic's Q/A for more on that), but I'm sure it does help if stress is impacting your memory.

No... actually my statements/opinions on nootropics almost never come from personal experience, only what is in the scientific literature, usually primary literature. Whenever piracetam is compared to another nootropic on a certain test, it is almost always active but weaker, not just in terms of potency but in terms of total effect. For example when we compare piracetam and aniracetam we find that aniracetam is more effective than piracetam in multiple animal models, and in the research that we do have on humans, aniracetam gives a greater effect on many tests of learning, memory, and mood than standard doses of piracetam. In sheer quantity of literature, piracetam has all the other nootropics beat, but I don't think that's a good measure of the strength of a nootropic.

No... actually my statements/opinions on nootropics almost never come from personal experience, only what is in the scientific literature, usually primary literature.

My statements come from a combination of reviewing studies, my patients, and my experience (15+).

Whenever piracetam is compared to another nootropic on a certain test, it is almost always active but weaker, not just in terms of potency but in terms of total effect.

For example when we compare piracetam and aniracetam we find that aniracetam is more effective than piracetam in multiple animal models, and in the research that we do have on humans, aniracetam gives a greater effect on many tests of learning, memory, and mood than standard doses of piracetam.

Based on the studies aniracetam appears better than piracetam in many areas, needed a lower dose, but I cannot find any studies showing any effects on healthy people, also there are many studies showing the various effects of piracetam on the brain and body, while very few studies showing all the of same effects from aniracetam.

In sheer quantity of literature, piracetam has all the other nootropics beat, but I don't think that's a good measure of the strength of a nootropic.

Here is where many people get confused of the purpose or reasons for taking nootropics is not merely the effect that is "felt" its the actually effects it is having in the brain both short and long term. While many newer nootropics appear to be more potent in 1 or 2 area of testing, most of them have very few studies done to ascertain their full effects in the brain. Because Piracetam has been around for over 30 years and 1,000’s of studies have been done we know most of the effects it has, a few studies showing aniracetam is more potent for than piracetam does not convince me it is automatically better or “stronger” aside from taking less pills.

A good example is comparing Huperzine A and Galantamine both block the breakdown of Acetylcholine, but Hup A does it at 1/100 the dose as galantamine, is Huperzine A stronger? Well yes and no, if by stronger you take less pills, but galantamine has additional effects that huperzine A does not have which can make it stronger or better for some people or other it just causes nausea.

So I agree with the new racetams that you take less of a dose and they appear “stronger” but unless all the effects piracetam offers is given from aniracetam, oxiracetam, or pramiracetam. I’ll keep taking my piracetam. Aniracetam does appear to have some slightly different effects so I do think its worth taking.

It is interesting to note that of all the racetams only piracetam is still putting out new studies, not bad for a weaker nootropic.


I was going to ask why your company sells piracetam and not the other forms?

Edited by LifeMirage, 19 September 2005 - 10:26 AM.

Based on the studies aniracetam appears better than piracetam in many areas, needed a lower dose, but I cannot find any studies showing any effects on healthy people, also there are many studies showing the various effects of piracetam on the brain and body, while very few studies showing all the of same effects from aniracetam.

As I said, piracetam has been researched much more extensively. On the other hand, we have a much better idea of the mechanism of action of aniracetam, as the pathways have been relatively well-laid out, while none of the research agrees on how piracetam works. This is probably because a lot of the research on the mechanism of action of aniracetam comes from more recent years in which we have had a much better understanding of how the brain works, while the majority of the research on the mechanism of action of piracetam is now obsolete.

Also, just because the research does not exist, does not mean one can assume an absence of effect. This especially applies to the nootropic effect - sure, piracetam has proven beneficial to the treatment of many conditions, which does not necessarily apply to a discussion of which is the stronger nootropic. In geriatrics, aniracetam has been found to be more effective than piracetam. It also caused greater changes in the EEG. In every animal study where they have been compared, including studies on antidepressant and anxiolytic effects, aniracetam yields a greater benefit. So I don't really think it is presumptious to call it a stronger nootropic, although I agree that it is not as well-established. It has still been studied extenesively enough to know that the nootropic effects are reliable.

I do think there are some reasons piracetam can be preferable, for example, the longer half-life, and it is less stimulating.

I was going to ask why your company sells piracetam and not the other forms?

Well piracetam came first because it was most well-known. We're working on getting some others. There are a lot of issues to be worked out though.

As I said, piracetam has been researched much more extensively. On the other hand, we have a much better idea of the mechanism of action of aniracetam, as the pathways have been relatively well-laid out, while none of the research agrees on how piracetam works. This is probably because a lot of the research on the mechanism of action of aniracetam comes from more recent years in which we have had a much better understanding of how the brain works, while the majority of the research on the mechanism of action of piracetam is now obsolete.

Most research (which is still ongoing unlike aniracetam, which confuses me when you say the research on piracetam is obsolete) has shown many different effects of how Piracetam works, The researchers you do the studies don't realize it's the combination of all the known effects of Piracetam that account for its nootropic and other actions. As far as Aniracetam I have not found any research showing anywhere near the # of known biochemical effects Piracetam has. If you can find the studies that show Aniracetam can:

[-Enhances Brain Metabolism (By increasing Glucose Utilization, Blood & Oxygen Flow) [Boosts mental energy & cerebral circulation].

-Increases Cerebral Phospholipids & Cellular Membrane Fluidity (By interacting with the polar head moieties of the phospholipid bilayer) [Supports healthy neuron communication & structure].

-Supports Cognitive Receptors (By amplifying the density of the Muscarinic Cholinergic [Frontal Cortex, Striatum, & Hippocampus], NMDA (N-Methyl-D-Aspartate) [Hippocampus], & AMPA (Alpha-amino-3-hydroxy-5-Methyl-4-isoxazole-Propionic Acid) [Cerebral Cortex] Receptors) [Strengthens neurotransmitter receptors involved in memory and neuroprotection].

-Stimulates the Corpus Callosum, an area of the brain that controls communication between the left and right hemispheres (Increases communication between both hemispheres) [Involved in speech and creative thinking].

- Stimulates the Locus Coeruleus, (specialized neurons) [Involved in information processing, attention, cortical/behavioral arousal, learning and memory]

-Inhibits Platelet Aggregation (By increasing Red-White blood cells & Platelet deformability, inhibiting thromboxane A2 synthetase or antagonism of thromboxane A2, reducing von Willebrand's factor & fibrinogen levels) [Reduces abnormal blood clots].

-Decreases EEG complexity (Increases cooperatively of brain functional processing) [Positively effects Neuro-Electrical Functioning].

-Has a significant antioxidant effect.]

I would to see it, but I'm not aware of any. Note: Aniracetam could be stronger in every aspect of a nootropic, but until the studies prove it I'm can't really say it's a better nootropic, stronger in some areas sure, but does everything & better than Piracetam doubtful.


We'll have to agree to disagree in this case.

Edited by LifeMirage, 19 September 2005 - 10:27 AM.

Most research (which is still ongoing unlike aniracetam, which confuses me when you say the research on piracetam is obsolete)

In medicine, research that is over five years old is generally considered obsolete. This is because our knowledge of the systems at work increases at an exponential rate. Although older research can be useful, it is not as reliable, especially when it comes to pharmacology studies on systems that we now know much more about. The last studies that took a good look at the molecular mechanisms of piracetam's action were done in 1999, all we have since that point are a few scattered comments and EEG studies. There are plenty of clinical trials, but these do not establish a mechanism of action, only efficacy in treating a certain condition. In contrast, the following studies on aniracetam primarily concerned with the mechanism of action have been published in the last two years:

Brain Res Mol Brain Res. 2003 Sep 10;117(1):91-6. 2-pyrrolidinone induces a long-lasting facilitation of hippocampal synaptic transmission by enhancing alpha7 ACh receptor responses via a PKC pathway. Miyamoto H, Yaguchi T, Ohta K, Nagai K, Nagata T, Yamamoto S, Nishizaki T.

Mol Pharmacol. 2003 Aug;64(2):269-78. The mechanism of action of aniracetam at synaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors: indirect and direct effects on desensitization. Lawrence JJ, Brenowitz S, Trussell LO.

J Neurochem. 2003 May;85(4):978-87. Facilitation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor transmission in the suprachiasmatic nucleus by aniracetam enhances photic responses of the biological clock in rodents. Moriya T, Ikeda M, Teshima K, Hara R, Kuriyama K, Yoshioka T, Allen CN, Shibata S.

Neurosci Lett. 2003 Mar 27;339(3):187-90. Effects of aniracetam on extracellular levels of transmitter amino acids in the hippocampus of the conscious gerbils: an intracranial microdialysis study. Yu S, Cai J.

Hippocampus. 2002;12(1):76-85. Aniracetam improves contextual fear conditioning and increases hippocampal gamma-PKC activation in DBA/2J mice. Smith AM, Wehner JM.

Pharmacol Biochem Behav. 2002 May;72(1-2):45-53. Cholinergic and dopaminergic mechanisms involved in the recovery of circadian anticipation by aniracetam in aged rats. Tanaka Y, Kurasawa M, Nakamura K.

Neurosci Lett. 2002 Mar 8;320(3):109-12. Aniracetam enhances glutamatergic transmission in the prefrontal cortex of stroke-prone spontaneously hypertensive rats. Togashi H, Nakamura K, Matsumoto M, Ueno K, Ohashi S, Saito H, Yoshioka M.

Brain Res Mol Brain Res. 2002 Jan 31;98(1-2):130-4. The aniracetam metabolite 2-pyrrolidinone induces a long-term enhancement in AMPA receptor responses via a CaMKII pathway. Nishizaki T, Matsumura T.

The researchers you do the studies don't realize it's the combination of all the known effects of Piracetam that account for its nootropic and other actions.

The idea that there are a number of mechanisms of action for piracetam has been explored and pretty much rejected. Any substance that effects one system is going to effect many others. The key is finding the original effect. With piracetam, that hasn't really been established. One of the main things that suggests that the mode of action of piracetam is singular is that the dose-response curve follows a classic bell shape. If a drug works through multiple mechanisms, you would not expect a bell shape, but a more complex dose-respone curve. Further support for a singular mechanism of action is provided by the fact that some things completely block the nootropic effect of piracetam - corticosteroid blockade and NMDA antagonists, for example. If a drug functions via multiple mechanisms, you would only expect to be able to partially block the effect via a singular process. The Gouliaev review provides additional support for the idea that racetam compounds tend to have specific mechanisms of action such as stereospecifity (as is the case with etiracetam) and the identification of specific binding sites.

As far as Aniracetam I have not found any research showing anywhere near the # of known biochemical effects Piracetam has.

But that's the key to understanding: Consistency and replication. One researcher concludes that the action of piracetam is primarily cholinergic, another concludes that the cholinergic system has nothing to do with it. One finds that increases monoamine levels, another finds a decrease. The same goes for many other explored mechanisms of piracetam, there is no consistency in the research. One of the reasons is that many of the models originally used in exploring the mechanism of piracetam are largely outdated. And, the fact that many of these effects you refer to were so reliant on experimental design would indicate that they are not the primary mode of action, but far downstream of a more specific effect.

[-Enhances Brain Metabolism (By increasing Glucose Utilization, Blood & Oxygen Flow) [Boosts mental energy & cerebral circulation].

-Increases Cerebral Phospholipids & Cellular Membrane Fluidity (By interacting with the polar head moieties of the phospholipid bilayer) [Supports healthy neuron communication & structure].

-Supports Cognitive Receptors (By amplifying the density of the Muscarinic Cholinergic [Frontal Cortex, Striatum, & Hippocampus], NMDA (N-Methyl-D-Aspartate) [Hippocampus], & AMPA (Alpha-amino-3-hydroxy-5-Methyl-4-isoxazole-Propionic Acid) [Cerebral Cortex] Receptors) [Strengthens neurotransmitter receptors involved in memory and neuroprotection].

-Stimulates the Corpus Callosum, an area of the brain that controls communication between the left and right hemispheres (Increases communication between both hemispheres) [Involved in speech and creative thinking].

- Stimulates the Locus Coeruleus, (specialized neurons) [Involved in information processing, attention, cortical/behavioral arousal, learning and memory]

-Inhibits Platelet Aggregation (By increasing Red-White blood cells & Platelet deformability, inhibiting thromboxane A2 synthetase or antagonism of thromboxane A2, reducing von Willebrand's factor & fibrinogen levels) [Reduces abnormal blood clots].

-Decreases EEG complexity (Increases cooperatively of brain functional processing) [Positively effects Neuro-Electrical Functioning].

-Has a significant antioxidant effect.]

None of these really describe the original effect. While they may describe an effect of the drug, they do not describe what it does at the molecular level. For example, what receptors or enzymes it modulates, and how it does so, preferably along with a structure-activity relationship. Example: Aniracetam is a dual positive allosteric modulator of AMPA receptors, specifically GluR1-flip, GluR1-flop, and GluR3-flop subunits. That is quite specific - not only does it give the specific receptor aniracetam acts at, but it differentiates it from other positive AMPA modulators in multiple ways, and is supported by a large amount of in vitro and in vivo experimental evidence. Stuff like "supports cognitive receptors" is something one says when they have no idea what is really going on.

Note: Aniracetam could be stronger in every aspect of a nootropic, but until the studies prove it I'm can't really say it's a better nootropic, stronger in some areas sure, but does everything & better than Piracetam doubtful.

Agreed - but my main reason for not assuming that aniracetam covers all that piracetam does is lack of information about piracetam, not vice versa. If we were to have a better understanding of how it works, it would give us a better understanding of the similarities and differences in activity between the two drugs, and it would be easier to determine if aniracetam will have all or most of the properties that piracetam does. For learning/memory improvement I tend to think aniracetam or a combination of the two is a better choice - because although aniracetam has not been tested in healthy humans, it has been superior to piracetam in just about every other population tested (including geriatrics, healthy adult primates, and other animal species), and that is good enough for me. However, if you are looking to treat vertigo or alcohol withdrawal, I would go with something like piracetam, because there is clinical support, while there is very little support for use of aniracetam for those purposes at this point.

[quote]In medicine, research that is over five years old is generally considered obsolete.[/quote]

Research old or new is information which is never obsolete.

This is because our knowledge of the systems at work increases at an exponential rate. Although older research can be useful, it is not as reliable, especially when it comes to pharmacology studies on systems that we now know much more about. [quote]The last studies that took a good look at the molecular mechanisms of piracetam's action were done in 1999, all we have since that point are a few scattered comments and EEG studies.[/quote]

Well considering there is no more profit in it I'm not surprised. Plus it’s been around for 30 years. Very few drugs are still being studied for that long.

There are plenty of clinical trials, [quote]but these do not establish a mechanism of action, only efficacy in treating a certain condition. In contrast, the following studies on aniracetam primarily concerned with the mechanism of action have been published in the last two years:[/quote]

Most of the clinical studies don't go into mechanism of action, they usually focus on effects. Well glad to know what effects it has in animals but I prefer long term human studies. Normally a drug is researched for actions first then clinical effects, considering they just started 2 years ago on aniracetam they have many years to go to do some good human studies.

QUOTE
The researchers you do the studies don't realize it's the combination of all the known effects of Piracetam that account for its nootropic and other actions.

[quote]The idea that there are a number of mechanisms of action for piracetam has been explored and pretty much rejected.[/quote]

I completely disagree with you on this, they shown that piracetam "has" a number of actions, but like most drug minded people they believe in the 1 drug has 1 action for 1 disease theory, which I believe is seriously flawed.

[quote]Any substance that effects one system is going to effect many others. The key is finding the original effect..[/quote]

That makes little good sense implying that all drugs have only 1 real effect that effects everything else.

[quote]With piracetam, that hasn't really been established.[/quote]

As far as studies focusing on its action yes far more the Aniracetam and most other nootropics.

One of the main things that [quote]suggests [/quote]that the mode of action of piracetam is singular is that the dose-response curve follows a classic bell shape. If a drug works through multiple mechanisms, you would not expect a bell shape, but a more complex dose-respone curve.

Try proving [quote]suggusts[/quote], suggusts you really don't know.

[quote]Further support for a singular mechanism of action is provided by the fact that some things completely block the nootropic effect of piracetam - corticosteroid blockade and NMDA antagonists, for example.If a drug functions via multiple mechanisms, you would only expect to be able to partially block the effect via a singular process.[/quote]

They block the noticeable effect of Piracetam on memory but by no means do they block all of piracetam nootropic effects in the brain.


QUOTE
As far as Aniracetam I have not found any research showing anywhere near the # of known biochemical effects Piracetam has.


[quote]But that's the key to understanding: Consistency and replication. One researcher concludes that the action of piracetam is primarily cholinergic, another concludes that the cholinergic system has nothing to do with it. One finds that increases monoamine levels, another finds a decrease. The same goes for many other explored mechanisms of piracetam, there is no consistency in the research. One of the reasons is that many of the models originally used in exploring the mechanism of piracetam are largely outdated. And, the fact that many of these effects you refer to were so reliant on experimental design would indicate that they are not the primary mode of action, but far downstream of a more specific effect.[/quote]

Here's the one aspect I can see how you are viewing it, Piracetam has ALL of these effects, there is no one magic bullet smart drug, not yet anyways. Drug mined people always keep looking for an answer when it's right in front of them.



QUOTE
[-Enhances Brain Metabolism (By increasing Glucose Utilization, Blood & Oxygen Flow) [Boosts mental energy & cerebral circulation].

-Increases Cerebral Phospholipids & Cellular Membrane Fluidity (By interacting with the polar head moieties of the phospholipid bilayer) [Supports healthy neuron communication & structure].

-Supports Cognitive Receptors (By amplifying the density of the Muscarinic Cholinergic [Frontal Cortex, Striatum, & Hippocampus], NMDA (N-Methyl-D-Aspartate) [Hippocampus], & AMPA (Alpha-amino-3-hydroxy-5-Methyl-4-isoxazole-Propionic Acid) [Cerebral Cortex] Receptors) [Strengthens neurotransmitter receptors involved in memory and neuroprotection].

-Stimulates the Corpus Callosum, an area of the brain that controls communication between the left and right hemispheres (Increases communication between both hemispheres) [Involved in speech and creative thinking].

- Stimulates the Locus Coeruleus, (specialized neurons) [Involved in information processing, attention, cortical/behavioral arousal, learning and memory]

-Inhibits Platelet Aggregation (By increasing Red-White blood cells & Platelet deformability, inhibiting thromboxane A2 synthetase or antagonism of thromboxane A2, reducing von Willebrand's factor & fibrinogen levels) [Reduces abnormal blood clots].

-Decreases EEG complexity (Increases cooperatively of brain functional processing) [Positively effects Neuro-Electrical Functioning].

-Has a significant antioxidant effect.]


[quote]None of these really describe the original effect.[/quote]

Still looking?

[quote]While they may describe an effect of the drug, they do not describe what it does at the molecular level.[/quote]

Umm yes its does, I should know I wrote it for them. It's a bit basic but it lists all the known molecular & biochemical effects (that I could find), which includes the nootropic effects.

For example, what receptors or enzymes it modulates, and how it does so, preferably along with a structure-activity relationship. Example: Aniracetam is a dual positive allosteric modulator of AMPA receptors, specifically GluR1-flip, GluR1-flop, and GluR3-flop subunits. That is quite specific - not only does it give the specific receptor aniracetam acts at, but it differentiates it from other positive AMPA modulators in multiple ways, and is supported by a large amount of in vitro and in vivo experimental evidence.

[quote]Stuff like "supports cognitive receptors" is something one says when they have no idea what is really going on.[/quote]

Oh I'm sure most people would understand this: (Piracetam amplifys the density of the Muscarinic Cholinergic [ only in the Frontal Cortex, Striatum, & Hippocampus], NMDA (N-Methyl-D-Aspartate) [Hippocampus], & AMPA (Alpha-amino-3-hydroxy-5-Methyl-4-isoxazole-Propionic Acid) [ in the Cerebral Cortex] Receptors)

In layman's terms [Strengthens neurotransmitter receptors involved in memory and neuroprotection].

QUOTE
Note: Aniracetam could be stronger in every aspect of a nootropic, but until the studies prove it I'm can't really say it's a better nootropic, stronger in some areas sure, but does everything & better than Piracetam doubtful.


[quote]Agreed - but my main reason for not assuming that aniracetam covers all that piracetam does is lack of information about piracetam, not vice versa.[/quote]

I would have to disagree Aniracetam in my opinion has been poorly studied as far as how it works compared to Piracetam, but it does not mean it can't be helpful until we get a better understanding of how it works (or they both work), but considering both patents have wored off and the little interest it's may not ever happen.

If we were to have a better understanding of how it works, it would give us a better understanding of the similarities and differences in activity between the two drugs, and it would be easier to determine if aniracetam will have all or most of the properties that piracetam does. For learning/memory improvement I tend to think aniracetam or a combination of the two is a better choice - [quote]because although aniracetam has not been tested in healthy humans, it has been superior to piracetam in just about every other population tested (including geriatrics, healthy adult primates, and other animal species),[/quote]

Superior as the reseachers (in the very few studies acutally done) compared them looking at isolated effects not total on the brain. It's like studing a memory drug with one that helps concretration and looking only at concretration, the concretation drugs is "superior". The studies only show in some effects Aniractam appears stronger.

[quote]and that is good enough for me. However, if you are looking to treat vertigo or alcohol withdrawal, I would go with something like piracetam, because there is clinical support, while there is very little support for use of aniracetam for those purposes at this point. [/quote]

There is every little support for aniracetam for any use at this point (The point could be made considering the small amount of studies of all types not just clinical), but using all the information we have I consider it one of better & safe tools we have available for now. As far as people using it as a nootropic if the effects give you want you want by all means use it, just make sure you’ve tried other nootropic so you know which one or combination is best for you.

Edited by LifeMirage, 10 May 2004 - 11:43 AM.

what does phenibut taste like? is it possible to mix with water and drink without being pestered by it's taste?

what does phenibut taste like? is it possible to mix with water and drink without being pestered by it's taste?

Doesn't taste that bad, I can handle it in water pretty easily, and you can barely taste in when mixed with something flavored.

what does phenibut taste like? is it possible to mix with water and drink without being pestered by it's taste?

Tastes almost bitter to me but not a bad taste though.. I mixed it with water when i first took it and it seems to disolve all the way (there didnt seem to be any residue left in the cup after i drank the water)

I'd add salty to the taste after pouring it directly on to my tongue. Maybe it reminds me of baking soda?

Anyway, from some of the descriptions I was expecting much worse (I've had much, much worse).

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hey sphongled! I've bought from bulknutrition, also a bodybuilder Glad to have you around. Was just thinking of using phenibut.