|This article relies too much on references to primary sources. (January 2015)|
|Systematic (IUPAC) name|
|Biological half-life||5.3 hours|
|Synonyms||Fenibut, Fenigam, Phenigam, Phenybut, Phenygam, Phenylgamma, PHG, PhGABA|
|Molecular mass||179.216 g/mol|
|Melting point||253 °C (487 °F)|
|(what is this?)|
Phenibut (or, alternatively, fenibut, phenybut) (brand name Noofen, Citrocard), contracted from β-phenyl-γ-aminobutyric acid (β-phenyl-GABA), is a central depressant and 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. Phenibut was developed in the Soviet Union in the 1960s, and has since been used there as a pharmaceutical drug to treat a wide range of ailments, including posttraumatic stress disorder, anxiety, depression, asthenia, insomnia, alcoholism, stuttering, and vestibular disorders, among other conditions. In the rest of the world, phenibut is not approved for clinical use, and is instead sold as a nutritional supplement. It has been reported by some researchers to possess nootropic actions for its ability to improve neurological functions,[medical citation needed] but others have not observed these effects. It is generally accepted that phenibut has anxiolytic effects in both animal models and in humans.
Phenibut is a close structural analogue of GABA, as well as of baclofen (β-(4-chlorophenyl)-GABA), pregabalin (β-isobutyl-GABA), and GABOB (β-hydroxy-GABA). Originally thought to act as a selective GABAB receptor agonist, phenibut has since been found to act preferentially as a blocker of α2δ subunit-containing voltage-gated calcium channels, similarly to gabapentin and pregabalin. As such, phenibut is a gabapentinoid.
Phenibut was synthesized at the A. I. Herzen Leningrad Pedagogical Institute (USSR) by Professor Vsevolod Perekalin's team and tested at the Institute of Experimental Medicine, USSR Academy of Medical Sciences.
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.[medical citation needed] In 1975 phenibut was included in the cosmonauts' kit for those who participated in the Apollo-Soyuz joint mission.
In terms of chemical structure, phenibut is a derivative of GABA with a phenyl group in the β-position. It is a chiral molecule and thus has two potential configurations, an (R)- and (S)-enantiomer. It has almost the same structure of baclofen (lacking only a chlorine atom in the para-position of the phenyl group) and contains phenethylamine in its structure. Pregabalin has the same structure as phenibut except that the phenyl group is instead an isobutyl group.
Phenibut hydrochloride is a white crystalline powder and the taste is very sour. It is readily soluble in water and in alcohol, and the pH of a 2.5% water solution is about 2.3–2.7.
Phenibut acts as an agonist of the GABAB receptor (specifically, a full agonist), similarly to baclofen and γ-hydroxybutyric acid (GHB), and at higher doses also of the GABAA receptor. It has some 30- to 68-fold lower affinity for the GABAB receptor relative to baclofen, which is active at far lower doses in comparison.
There is dispute in the literature about whether or not phenibut binds to the GABAA receptor, which is the receptor responsible for the actions of the benzodiazepines, barbiturates, and Z-drugs, and for the main effects of ethanol. According to Allikmets and Ryage (1983) and Shulgina (1986), phenibut does bind to the GABAA receptor, but according to Lapin (2001), it does not. In the case of the former, it is argued that the GABAA binding only occurs at higher concentrations.
The literature that supports the nootropic effects of phenibut also suggest that it elicits tranquilizing effects, reduction of stress and anxiety, improvement of impaired sleep, and the potentiation (enhancement) of the effects of tranquilizers, narcotics, and neuroleptics. It is also suggested to have an anticonvulsant effect, though studies on other GABAB agonists, such as GHB and the phenibut analogue baclofen, have shown them to act as potential convulsants. It should be noted, however, that GHB acts on the convulsion-inducing GHB receptor, which phenibut does not.
Recently, it has been found that phenibut binds to and blocks α2δ subunit-containing voltage-gated calcium channels (VGCCs), similarly to gabapentin and pregabalin. Both enantiomers of phenibut show this action with similar efficacy. Moreover, the R-enantiomer possesses five-fold greater affinity for this site relative to the GABAB receptor, while the S-enantiomer does not bind to the GABAB receptor. As such, phenibut is likely to have much greater effect on α2δ subunit-containing VGCCs than on the GABAB receptor. Notably, the antinociceptive effects of phenibut in rodents are mediated not by the GABAB receptor but by blockade of α2δ subunit-containing VGCCs.
For medical use, phenibut is generally prescribed at a dosage of 250–1500 mg twice a day.
The side effects of phenibut are said to be similar to but milder than those of baclofen. They include sleepiness and hangover-like effects such as headache and depression once the drug has worn off.
Limited evidence indicates that withdrawal symptoms of phenibut include severe anxiety, nervousness, tremors, agitation, dizziness, irritation, fatigue, loss of appetite, rapid heartbeat, nausea, vomiting, tension, psychosis, hallucinations, and insomnia. These effects may last for up to two weeks. Tolerance may develop rapidly with repeated use.
Phenibut should not be combined with alcohol, sedatives, monoamine oxidase inhibitors, anticonvulsants like carbamazepine, or other prescription drugs. Persons on such medications should consult with their medical practitioners prior to taking phenibut. Evidence suggests that phenibut can modulate the function of some epilepsy medications.
- 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.
- Smirnova LA, Perfilova VN, Tyurenkov IN, Ryabukha AF, Suchkov EA, Lebedeva SA (2013). "Study of the absolute bioavailability of citrocard, a new GABA derivative". Bull. Exp. Biol. Med. 155 (4): 458–60. PMID 24143367.
- J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 69–. ISBN 978-1-4757-2085-3.
- 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.
- David W. Group (25 February 2015). Encyclopedia of Mind Enhancing Foods, Drugs and Nutritional Substances, 2d ed. McFarland. pp. 186–. ISBN 978-0-7864-4142-6.
- Nelson, LS (2008). "Phenibut Withdrawal - A Novel 'Nutritional Supplement'". Clinical Toxicology 46 (7): 605. doi:10.1080/15563650802255033.
- Kovaleva, E. L. (1984). "Comparative characteristics of the nootropic action of fenibut and fepiron". Farmakologiia i toksikologiia 47 (1): 20–23. PMID 6705902.
- Lapin I (2001). "Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug". CNS Drug Rev 7 (4): 471–81. PMID 11830761.
- Zvejniece, Liga; Vavers, Edijs; Svalbe, Baiba; Veinberg, Grigory; Rizhanova, Kristina; Liepins, Vilnis; Kalvinsh, Ivars; Dambrova, Maija (2015). "R-phenibut binds to the α2–δ subunit of voltage-dependent calcium channels and exerts gabapentin-like anti-nociceptive effects". Pharmacology Biochemistry and Behavior 137: 23–29. doi:10.1016/j.pbb.2015.07.014. ISSN 0091-3057.
- Elaine Wyllie; Gregory D. Cascino; Barry E. Gidal; Howard P. Goodkin (17 February 2012). Wyllie's Treatment of Epilepsy: Principles and Practice. Lippincott Williams & Wilkins. p. 423. ISBN 978-1-4511-5348-4.
- Honorio Benzon; James P. Rathmell; Christopher L. Wu; Dennis C. Turk; Charles E. Argoff; Robert W Hurley (11 September 2013). Practical Management of Pain. Elsevier Health Sciences. p. 1006. ISBN 978-0-323-17080-2.
- Slava Lapin (30 July 2009). From the Inside. Luniver Press. p. 209. ISBN 978-1-905986-11-8. Retrieved 6 November 2010.
- 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.
- GABAb Receptor Pharmacology: A Tribute to Norman Bowery: A Tribute to Norman Bowery. Academic Press. 21 September 2010. pp. 25–. ISBN 978-0-12-378648-7.
- Zyablitseva, Evgeniya A.; Kositsyn, Nikolay S.; Shul'gina, Galina I. (2013). "The Effects of Agonists of Ionotropic GABAA and Metabotropic GABAB Receptors on Learning". The Spanish journal of psychology 12 (01): 12–20. doi:10.1017/S1138741600001438. ISSN 1138-7416.
- 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.
- Wong A, Little M, Caldicott D, Easton C, Andres D, Greene SL (2015). "Analytically confirmed recreational use of Phenibut (β-phenyl-γ-aminobutyric acid) bought over the internet". Clin Toxicol (Phila) 53 (7): 783–4. doi:10.3109/15563650.2015.1059944. PMID 26107626.
- 4-Amino-3-phenylbutyric acid in the ChemIDplus database