Phenibut
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|---|---|
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| Systematic (IUPAC) name | |
| (RS)-4-amino-3-phenyl-butyric acid | |
| Clinical data | |
| Trade names | Noofen |
| Legal status | OTC (US) |
| Routes | Oral |
| Pharmacokinetic data | |
| Half-life | 5 hours |
| Identifiers | |
| CAS number | 1078-21-3  |
| ATC code | N06BX22 |
| PubChem | CID 14113 |
| ChemSpider | 13491  |
| ChEMBL | CHEMBL315818 |
| Synonyms | Fenibut, Phenybut, PhGABA |
| Chemical data | |
| Formula | C10H13NO2 |
| Mol. mass | 179.216 g/mol |
| SMILES
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| Physical data | |
| Melt. point | 253 °C (487 °F) |
| (what is this?) (verify) | |
β-Phenyl-γ-aminobutyric acid (brand name Noofen), better known as phenibut or less commonly fenibut or phenybut, is a derivative of the naturally occurring inhibitory neurotransmitter γ-aminobutyric acid (GABA). The addition of a phenyl ring allows phenibut to cross the blood brain barrier.[1] Phenibut is sold as a nutritional supplement,[2] and is not approved as a pharmaceutical in the United States or Europe, but in Russia it is sold as a psychotropic drug. It has been reported by some to possess nootropic actions for its ability to improve neurological functions,[3] but other researchers have not observed these effects.[4] It is generally accepted that phenibut has anxiolytic effects in both animal models and in humans.[1] Phenibut was discovered in the Soviet Union in the 1960s, and has since been used there to treat a wide range of ailments including post-traumatic stress disorder, anxiety, and insomnia.[3]
The name phenibut, along with many of the other names for the compound, comes directly from the chemical name for the compound, β-phenyl-γ-aminobutyric acid.
History
Phenibut was synthesized at the I. M. Herzen Leningrad Pedagogical Institute USSR and the Institute of Experimental Medicine, Academy of Medical Sciences USSR by Professor V. V. Perekalin's team.
Phenibut is mandated standard equipment in a Russian cosmonaut's medical kit. The use of "conventional" tranquilizers for stress and anxiety makes patients drowsy, which was deemed unacceptable for cosmonauts; phenibut, however, lowers stress levels without adversely affecting performance. In 1975 phenibut was included in the cosmonauts' kit for those who participated in the Apollo-Soyuz joint mission.[5]
General information
In chemical structure, phenibut is a phenyl derivative of GABA. Although the calming action is similar to other GABA agonists, phenibut binds to the GABAB metabotropic receptor, the same site responsible for the sedative effects of baclofen (the para-chloro derivative of phenibut) and γ-hydroxybutyrate (GHB), although GHB also acts at the GHB receptor.[6] There is dispute in the literature about whether or not phenibut binds to the GABAA ionotropic receptor, which is responsible for the actions of the benzodiazepines, barbiturates, z-drugs, and for some of the effects of ethanol. According to Allikmets and Ryage (1983) and Shulgina (1986) phenibut does bind to the GABAA receptor,[3] but according to Lapin (2001) it does not.[1] In the case of the former, it is argued that the GABAA binding only occurs at higher concentrations.[3]
The literature that supports the nootropic effects of phenibut also suggest it elicits tranquilizing effects,[1] reduction of stress and anxiety, improvement of impaired sleep, and the potentiation of the effects of tranquilizers, narcotics, and neuroleptics. It is also suggested to have an anticonvulsant effect,[3] though studies on other GABAB agonists, such as GHB and the phenibut analogue baclofen, have shown them to act as potential convulsants.[citation needed] It should be noted, however, that GHB acts on the convulsion-inducing GHB receptor,[7] which phenibut does not.
Physical properties
Phenibut HCl is a white crystalline powder and the taste is very sour. It is readily soluble in water, soluble in alcohol, and the pH of a 2.5% water solution is between about 2.3 and 2.7.
Doses
Commonly recommended doses are 250–1500 mg, twice daily,[3][8] or as needed. This is up to the discretion of the health care practitioner as it pertains to patient needs. At doses above 40 mg/kg, a lowering of body temperature may occur along with muscle relaxation.[3][9]
Chemistry
Structurally, phenibut is a γ-aminobutyric acid with a phenyl group in the β-position. It is a chiral molecule and thus has two potential configurations, an (R)- and (S)-enantiomer. In phenibut, only the (R)-enantiomer is biologically active leaving the (S)-enantiomer of little value.[6] It has the same structure of baclofen[3] (lacking only a chlorine atom in the para-position of the phenyl group) and includes the phenylethylamine structure.
Pharmacology
The pharmacological effects of phenibut are similar to baclofen [citation needed], but less potent per milligram of dosage.
Phenibut exerts its effects by being an agonist at the metabotropic GABAB receptor, and at higher doses also at the ionotropic GABAA receptor.[3]
Some studies found that phenibut antagonizes the effects of phenylethylamine (PEA),[1][10] while others found no effect on PEA induced anxiety.[11]
Furthermore, phenibut has been shown to enhance levels of dopamine.[1]
Contraindications and side effects
There are numerous reports of withdrawal symptoms on Internet forums and blogs [2][12] including "nervousness and shakiness, psychomotor agitation, feeling easily annoyed and irritated, fatigue, poor appetite, heart pounding and racing, nausea, insomnia, and feeling tense and keyed up",[2] consistent with its GABAB agonist properties. There has been no systematic study of this problem.
Persons on MAO inhibitors or epilepsy medications like carbamazepine or oxcarbazepine should consult with their physician or pharmacist prior to supplementation with phenibut. Some evidence suggests that phenibut can modulate the function of some epilepsy medications.[3]
See also
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Lapin, I. (2001). "Phenibut (beta-phenyl-GABA): A tranquilizer and nootropic drug" (pdf). CNS Drug Reviews 7 (4): 471–481. doi:10.1111/j.1527-3458.2001.tb00211.x. PMID 11830761.
- ↑ 2.0 2.1 2.2 Nelson, LS (2008). "Phenibut Withdrawal - A Novel 'Nutritional Supplement'". Clinical Toxicology 46 (7): 605.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 3.9 Shulgina, G. I. (1986). "On neurotransmitter mechanisms of reinforcement and internal inhibition". The Pavlovian journal of biological science 21 (4): 129–140. doi:10.1007/BF02734511. ISSN 0093-2213. PMID 2431377.
- ↑ Kovaleva, E. L. (1984). "Comparative characteristics of the nootropic action of fenibut and fepiron". Farmakologiia i toksikologiia 47 (1): 20–23. PMID 6705902.
- ↑ Slava Lapin (30 July 2009). From the Inside. Luniver Press. p. 209. ISBN 978-1-905986-11-8. Retrieved 6 November 2010.
- ↑ 6.0 6.1 Dambrova, M.; Zvejniece, L.; Liepinsh, E.; Cirule, H.; Zharkova, O.; Veinberg, G.; Kalvinsh, I. (2008). "Comparative pharmacological activity of optical isomers of phenibut". European Journal of Pharmacology 583 (1): 128–134. doi:10.1016/j.ejphar.2008.01.015. PMID 18275958.
- ↑ Banerjee, P. K.; Snead Oc, 3. (1995). "Presynaptic gamma-hydroxybutyric acid (GHB) and gamma-aminobutyric acidB (GABAB) receptor-mediated release of GABA and glutamate (GLU) in rat thalamic ventrobasal nucleus (VB): A possible mechanism for the generation of absence-like seizures induced by GHB". The Journal of Pharmacology and Experimental Therapeutics 273 (3): 1534–1543. PMID 7791129.
- ↑ Makarov, V. I.; Tiurenkov, I. N.; Klauchek, S. V.; Nalivaĭko, I. O.; Antipova, A. U. (1997). "Experimental bases of the use of pharmacologic agents aimed at higher heat resistance of humans as means of individual protection". Meditsina truda i promyshlennaia ekologiia (5): 35–38. PMID 9235216.
- ↑ Khaunina, R. A. (1964). "Tranquilizing Effects of Beta-Phenyl-Gamma-Aminobutyric Acid (Fenigam)". Biulleten' eksperimental'noi biologii i meditsiny 57: 54–58. PMID 14162373.
- ↑ Lapin, I. P. (1985). "Differences and similarity in the interaction of fenibut, baclofen and diazepam with phenylethylamine". Farmakologiia i toksikologiia 48 (4): 50–54. PMID 4043364.
- ↑ Lapin, I. P.; Slepokurov, M. V. (1991). "The anxiogenic activity of phenylethylamine in the social isolation test on mice". Farmakologiia i toksikologiia 54 (6): 9–11. PMID 1804703.
- ↑ Fries, D (5 Nov 2012). "How To Avoid The Side Effects of Phenibut". The Nootropics Cabinet.
External links
- 4-Amino-3-phenylbutyric acid in the ChemIDplus database