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. 2006 Jun 7;7(4):471–481. doi: 10.1111/j.1527-3458.2001.tb00211.x

Phenibut (β‐Phenyl‐GABA): A Tranquilizer and Nootropic Drug

Izyaslav Lapin 1,
PMCID: PMC6494145  PMID: 11830761

ABSTRACT

Phenibut (β‐phenyl‐γ‐aminobutyric acid HCl) is a neuropsychotropic drug that was discovered and introduced into clinical practice in Russia in the 1960s. It has anxiolytic and nootropic (cognition enhancing) effects. It acts as a GABA‐mimetic, primarily at GABAB and, to some extent, at GABAA receptors. It also stimulates dopamine receptors and antagonizes β‐phenethylamine (PEA), a putative endogenous anxiogenic. The psychopharmacological activity of phenibut is similar to that of baclofen, a p‐Cl‐derivative of phenibut. This article reviews the structure‐activity relationship of phenibut and its derivatives. Emphasis is placed on the importance of the position of the phenyl ring, the role of the carboxyl group, and the activity of optical isomers. Comparison of phenibut with piracetam and diazepam reveals similarities and differences in their pharmacological and clinical effects. Phenibut is widely used in Russia to relieve tension, anxiety, and fear, to improve sleep in psychosomatic or neurotic patients; as well as a pre‐ or post‐operative medication. It is also used in the therapy of disorders characterized by asthenia and depression, as well as in post‐traumatic stress, stuttering and vestibular disorders.

Keywords: Amphetamine, Anxiety, Anxiolytic, Baclofen, Cognition enhancement, GABA, Nootropic, PEA, Phenethylamine, Phenibut

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References

  • 1. Allikmets LH, Polevoy LG, Tsareva TA, Zarkovsky AM. Dopaminergic component in the mechanism of action of derivatives and structural analogs of GABa. Farmakol Toksikol 1979;42:603–606 (n Russian with English summary). [PubMed] [Google Scholar]
  • 2. Allikmets LH, Rago LK, Nurk AM. Effect of bicuculline, a blocker of GABa receptors, on the effects of phenibut and diazepam. Byull Eksp Biol Med 1982;94:64–65 (n Russian with English summary). [Google Scholar]
  • 3. Allikmets LH, Zarkovsky AM, Nurk AM. Effect of cholino‐ and GABA‐ergic drugs on a neuroleptics‐induced syndrome of hypersensitivity of dopamine receptors. Trudy Tartu Gos Univ. Mechanism of Action of Psychotropic Drugs 1982;600:3–13 (n Russian with English summary). [Google Scholar]
  • 4. Anden N‐E, Wachtel H. Biochemical effects of baclofen (β‐parachlorophenyl‐GABA) on the dopamine and the noradrenaline in the rat brain. Acta Pharmacol Toxicol 1977;40:310–320. [DOI] [PubMed] [Google Scholar]
  • 5. Andreev BV, Belozertseva IV, Dunaevsky VV, Patkina NA, Tikhomirov SM. Effect of GABA‐ergic drugs on formation of opiate dependence and management of withdrawal syndrome in experiment and clinic In: Prophilaxis of relapses in alcoholism and narcomanias. St. Petersburg : Bekhterev Psychoneurological Institute; 1991:102–107 (in Russian with English summary) . [Google Scholar]
  • 6. Belozertseva IV, Andreeev BV. Effect of GABA‐positive agents on the development of morphine addiction and the cessation syndrome manifestations. Eksp Klin Farmakol 2000;63:19–23 (n Russian with English summary). [PubMed] [Google Scholar]
  • 7. Bowery NG. GABA‐B receptor pharmacology. Ann Rev Pharmacol Toxicol 1992;23:109–147. [DOI] [PubMed] [Google Scholar]
  • 8. Bowery NG, Hill DR, Hudson AL. [3H](‐)baclofen: An improved ligand for GABA‐B sites. Neuropharmacology 1985;24:207–210. [DOI] [PubMed] [Google Scholar]
  • 9. Bowery NG, Kerr DIB, Ong J. GABAB receptors: Role and therapeutic implications in CNS disorders. CNS Drugs 1997;7:167–175. [Google Scholar]
  • 10. Buu NT, VanGelder NM, Biological actions in vivo and in vitro of two γ‐aminobutyric acid (GABA) analogs: β‐chloro GABA and β‐phenyl GABA. Br J Pharmacol 1974;52:401–406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. Davies J, Watkins JC. The action of β‐phenyl‐GABA derivatives on neurons of cat cerebebral cortex. Brain Res 1974;70:501–505. [DOI] [PubMed] [Google Scholar]
  • 12. Dirig DM, Yaksh TL. Intrathecal baclofen and muscimol, but not midazolam, are antinociceptive using the rat‐formalin model. J Pharmacol Exp Ther 1995;275:219–227. [PubMed] [Google Scholar]
  • 13. Froestl W, Bettler B, Bittiger H, Held J, Kaupman K, Mickel SJ, Strub D. Ligands for the isolation of GABA(B) receptors. Neuropharmacology 1999;38:1641–1646. [DOI] [PubMed] [Google Scholar]
  • 14. Galli A, Zilletti L, Scotton M, Adembri G, Giotti A. Inhibition of Na‐independent [3H]GABA binding to synaptic membranes of rat brain by β‐substituted GABA derivatives. J Neurochem 1979;32:1123–1125. [DOI] [PubMed] [Google Scholar]
  • 15. Goldblat Yu V, Lapin IP. Potentiation of the therapeutic effect of antiparkinsonian drugs by phenibut. Zh Nevropatol Psikhiatrii 1986;86:1146–1148 (n Russian with English summary). [PubMed] [Google Scholar]
  • 16. Khaunma RA. Tranquillizing effects of β‐phenyl‐γ‐aminobutyric acid (“Phenigama”). Byull Eksp Biol Med 1964;1:54–58 (n Russian with English summary). [Google Scholar]
  • 17. Khaunina RA. Structure‐activity relationships among phenyl derivatives of γ‐aminobutyric acid. Farmakol Toksikol 1968;2:202–205 (n Russian with English summary). [PubMed] [Google Scholar]
  • 18. Khaunina RA. The pharmacological activity of optic isomers of beta‐phenyl‐gamma‐ammobutync acid. Byull Eksp Biol Med 1971;11:49–51 (n Russian with English summary). [PubMed] [Google Scholar]
  • 19. Khaunina RA, Lapin IP. Use of phenibut in psychoneurology and its place among other psychotropic drugs. Zh Nevropatol Psikhiatrii 1989;89:142–151 (n Russian with English summary). [PubMed] [Google Scholar]
  • 20. Khaunina RA, Prakhie I. B. Effect of phenibut on the action of anticonvulsants. Trudy Psikhonevrol Inst Bekhtereva 1969;52:382–384 (n Russian with English summary). [Google Scholar]
  • 21. Kovalev GI, Prihozan AV, Raevsky KS. Presynaptic component in the mechanism of action of phenibut. Byull Eksp Biol Med 1982;94:59–61 (n Russian with English summary). [PubMed] [Google Scholar]
  • 22. Kovalev GV, Ed. Pharmacology and clinic of gamma‐aminobutyric acid and its analogs. Volgograd : Izd. VMI, 1979. (in Russian with English summary) . [Google Scholar]
  • 23. Kovalev GV, Morozov IS. The effect of GABA and phenibut on neural vasomotor mechanisms. In: 6th Int. Congress of Pharmacololgy (Helsinki, July 20–25 , 1975). Abstracts: 1253.
  • 24. Kozlovskaya MM, Raevsky KS, Kovalev GI, Kharlamov AN. Comparison psychotropic and neurochemical action of phenibut Neuropharmacology (New drugs in neurology). Leningrad : Izd. IEM, 1980;81–82 (in Russian with English summary) . [Google Scholar]
  • 25. Kozlovsky VL, Gusel VA. Experimental study on antiepileptic action of phenibut. In: Abstrs. of the All‐Union Symposium “Phenibut and derivatives of GABA and α‐pyrrolidones (clinic, pharmacology, chemistry, industry)”. Tcherkassy : 1981;25–29 (in Russian with English summary).
  • 26. Krupitsky EM, Burakov AM, Ivanov VB, et al. Baclofen administration for the treatment of affective disorders in alcoholic patients. Drug Alcohol Dependence 1993;33:157–163. [DOI] [PubMed] [Google Scholar]
  • 27. Lapin IP. Phenibut and baclofen as antagonists of phenylethylamine. Trudy Tartu Gos Univ. Mechanism of action and clinic of derivatives of GABA 1984;687:36–44 (n Russian with English summary). [Google Scholar]
  • 28. Lapin IP. Dissimilarities and similarities between phenibut, baclofen and diazepam in interaction with phenylethylamine. Farmakol Toksikol 1985;48:50–54 (n Russian with English summary). [PubMed] [Google Scholar]
  • 29. Lapin IP. Pharmacological differences between kynurenine‐ and pentylenetetrazole‐induced seizures (participation of GABA‐B receptors and dopamine). Eksp Klin Farmakol 1998;61:20–22 (n Russian with English summary). [PubMed] [Google Scholar]
  • 30. Lapin IP. Beta‐phenylethylamine (PEA): An endogenous anxiogen? Three series of experimental data. Biol Psychiatry 1990;28:997–1003. [DOI] [PubMed] [Google Scholar]
  • 31. Lapin IP. Anxiogenic effect of phenylethylamine and amphetamine in the elevated plus‐maze in mice and its attenuation by ethanol. Pharmacol Bioch Behav 1992;44:241–243. [DOI] [PubMed] [Google Scholar]
  • 32. Lapin IP, Khaunina RA. Pharmacology and clinical use of gamma‐aminobutyric acid and its derivatives In: Role of gamma‐aminobutyric acid in the activity of the nervous system. Leningrad : Izd. LGU, 1964:101–115 (n Russian with English summary). [Google Scholar]
  • 33. Lapin IP, Krupitsky EM, Melnik VI, et al. Phenibut (β‐phenyl‐GABA) and baclofen (chlor‐Phenibut) in treatment of affective disorders in alcoholic patients. Alcohol Alcoholism 1995;30:549. [Google Scholar]
  • 34. Lapin IP, Slepokurov MV. Anxiogenic activity of phenylethylamine in a social interaction test. Farmakol Toksikol 1991;54:9–11 (n Russian with English summary). [PubMed] [Google Scholar]
  • 35. Malcangio M, Bowery NG. Possible therapeutic applications of GABA‐B receptor agonists and antagonists (review). Clin Neuropharmacol 1995;18:285–305. [DOI] [PubMed] [Google Scholar]
  • 36. Maslova MN, Khaunina RA Distribution of β‐phenyl‐γ‐aminobutyric acid in the body and certain indices of its central effects. Byull Eksp Biol Med 1965;8:65–69 (n Russian with English summary). [PubMed] [Google Scholar]
  • 37. Maslova MN, Khaunina RA Penetration of gamma‐aminobutyric acid and its phenyl derivative into the brain and their pharmacological effects in mice and rats during ontogenesis. Evol Neirofiziol Neirokhim 1967;5:186–191 (n Russian with English summary). [Google Scholar]
  • 38. Mehilane LS, Rago LK, Allikmets LH. Pharmacology and clinic of phenibut. Tartu : Izd. TGU, 1990. (in Russian with English summary) . [Google Scholar]
  • 39. Mutovkma LG, Lapin IP. Attenuation of effects of phenylethylamine on social and individual behavior in mice by ethanol pretreatment. Alcohol Alcoholism 1990;25:417–420. [PubMed] [Google Scholar]
  • 40. Novikov VE, Naperstnikov VV. Effect of phenibut on ultrastructure of brain mitochondria after traumatic oedema‐swelling. Eksp Klin Farmakol 1994;57:13–70 (n Russian with English summary). [PubMed] [Google Scholar]
  • 41. Ong J, Kerr DI. Recent advances in GABA(B) receptors: From pharmacology to molecular biology. Acta Pharmacol Sinica 2000;21:111–123. [PubMed] [Google Scholar]
  • 42. Orlikov AB. Comparison of efficacy of imipramine, diazepam, baclofen, propranolol and placebo in patients with panic disorders. Obozr Psikh Med Psikhol Bekhtereva 1994;4:43–48 (n Russian with English summary). [Google Scholar]
  • 43. Rago LK, Nurk AM, Korneev AY, Allikmets LH. Binding of phenibut with bicuculline‐insensitive GABA receptors in the rat brain. Byull Eksp Biol Med 1982;11:58–59 (n Russian with English summary). [PubMed] [Google Scholar]
  • 44. Shepard RA. Direct evidence for mediation of an anticonflict effect of baclofen by GABA‐B receptors. Pharmacol Bioch Behav 1992;41:651–653. [DOI] [PubMed] [Google Scholar]
  • 45. Stark MB, Danilyuk VP, Weisman NA, Zinevich VS Electrophysiological study on the central effects of gamma‐aminobutyric and beta‐phenyl‐gamma‐aminobutyric acids. Fiziol Zh 1967;13:154–164 (n Russian with English summary). [Google Scholar]
  • 46. Sulcova A, Krsiak M, Masek K. Effects of baclofen on agonistic behavior in mice. Activitas Nervosa Super (Prague) 1978;20:241–242. [PubMed] [Google Scholar]
  • 47. Talalaenko AN, Panfilov VYu, Vozdigan SA, Pokramovich AI, Markova OP, Okhrimenko SV. Neurochemical profile of septal nucleus accumbens in anxiolytic effect of tranquillizers on various anxiety models. Eksp Klin Farmakol 1997;60:7–9 (in Russian with English summary). [PubMed] [Google Scholar]
  • 48. Talalaenko AN, Gordienko DV, Markova OP. Neurochemical profile of caudate nucleus in anxiolytic effect of benzodiazepine and nonbenzodiazepine tranquillizers in different models of anxiety. Eksp Klin Farmakol 2000;63:14–18 (n Russian with English summary). [PubMed] [Google Scholar]
  • 49. Wang Y‐X, Bowersox SC. Analgesic properties of ziconotide, a selective blocker of N‐type neuronal calcium channels. CNS Drug Revs 2000;6:1–20. [Google Scholar]
  • 50. Zavadskaya LN. Effect of GABA and its derivatives on the ion channels of the membrane of identified neurons of Planorbarius corneus. Izv AN Kazakhstana Ser Biol 1984;6:13–19 (n Russian with English summary). [Google Scholar]

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