The initial chemical synthesis of Phenibut was done in the U.S.S.R. by Professor V.V. Perekalin and his team of researchers at the I.M. Herzen Leningrad Pedagogical Institute of experimental medicine. The team synthesized 3-phenyl-4-aminobutyric acid as an experimental drug to assist calm psychiatric children. It is said to possess nootropic properties, cognition enhancer, boosting capacity for intelligence, and enhances the ability to solve complex problems, but there is no substantial scientific evidence to back this effects. It is also thought to lower stress levels like a tranquilizer without exhibiting the drowsy or depressive side effects. Within Russia, Phenibut is mandatory standard equipment in the Russian Medical Kit.
In 1964, the drug was labeled as Phenigamma by Professor Khaunma who also reported observing tranquilizing effects of the drug. By 1975, Phenigamma had started being used by the public within Russia, and it was now known as Phenibut. At the same time, the Soviet Union mandated the use of Phenibut by astronauts in space flights because of the revolutionary psychologically calming and cognitive stimulating properties. There are multiple scientific publications on studies that examined the nootropic and pharmacological properties of Phenibut.
Phenibut is used and sold as a nutritional supplement. Within Europe and the United States, it has not yet been approved for use as a pharmaceutical drug. However, Russian authorities have approved its use and sale as a neuro-psychotropic drug. Russian scientists often use Phenibut because of its unique properties of lowering stress levels without having negative effects on performance levels. Most modern tranquilizers for stress and anxiety tend to cause drowsiness in patients, and this was considered unacceptable for cosmonauts. Phenibut is used globally as a smart drug, sleep aid, mood enhancer, and recovery booster.
In one scientific study, researchers sought to examine the stress relieving properties of beta-(phenyl) GABA by examining its influence on the central and peripheral-type benzodiazepine binding sites. The study conducted in Russia found that when rats were exposed to forced swimming stress, the stress lead to significant rise in the density of central type benzodiazepine binding sites within the rats' hippocampus and cerebral cortex. On the blood platelets, the quantity of peripheral-type benzodiazepine binding sites was also observed to undergo substantial enhancements. No considerable changes regarding the affinity of both peripheral and central type benzodiazepine binding sites were observed after the rats were exposed to swimming stress. In rats that were pretreated with 100mg/kg of beta-(phenyl)GABA (a GABAB agonist), it was observed to almost entirely eliminate the changes that were observed in the two types of benzodiazepine binding sites as a result of swimming stress. When effects were assessed using the elevated plus-maze model of anxiety, beta-(phenyl)GABA was observed to be ineffective although it behaved similarly to diazepam and efficiently led to a reversal of the behavioral properties of DMCM (a beta -carboline derivative which has anxiogenic properties).
In a guinea pig based study, researchers examined the variations in actions of both Phenibut and Baclofen. The two compounds were observed to induce a dose-dependent depression of cholinergic twitching contractions to transmural stimulation within the guinea pig isolated ileum, that was sensitive to phosphonobaclofen (phaclofen) and delta-aminoyaleric acid (DAVA). The Phenibut administration was observed to antagonize the depressant effect of Baclofen and GABA, and it additionally depressed (weakly) ileal twitch contractions whereby DAVA and phaclofen had no influence. These results indicated that baclofen receptors found in the ileum that are antagonized by Phenibut vary from both baclofen receptors found in the spinal cord (here the presynaptic receptors are blocked by phaclofen) and the postsynaptic receptors were not influenced by phaclofen, with Phenitub exhibiting baclofen-like actions in both sites. The variation in the therapeutic properties of the two compounds is explained by the interaction of Phenibut and baclofen with various receptor populations.
In another comparative experiment, the nootropic properties of Phenibut and phepyrone were evaluated and contrasted when administered to rats in low dosages. Experiments conducted in a shuttle box and water maze indicated that both piracetam and phepyrone enhanced the learning performance in rats but Phenibut was observed not to have any nootropic properties in the doses tested. In experiments involving rats, acute and chronic administration of phenibut and phenibut esters, it was established that phenibut ethers have a higher potency of about 7-10 times that of phenibut itself when tested for hypotensive activity and had inconsistent effects on hemodynamics and cardio-dynamics. Among the ethers, the methyl ether of phenibut was observed to be the most powerful agent with a lasting hypotension when administered in doses of 1/30 and 1/50 of the LD50 but the peripheral resistance was observed to decrease. In addition to increasing the blood inflow to the heart and cardiac output, the substance was observed to compensate adverse inotropic and chronotropic action of the heart.
In a particular scientific study, the Mg2+ -ATPase activity was observed in the cortex mitochondrial fraction, medulla oblongata, and limbic system when exposed to conditions of chronic stress and a prior preliminary treatment with psychotropic drugs. During the inanition phase in the animals, the chronic stress was observed to inhibit harshly the process of phosphorylation and respiration as well as lower the content of brain macroergs. As a result, the Mg2+ -ATPase activity within the mitochondria was observed to drop. I was observed to restore the degree of control alongside a background of stress upon preliminary administration of GABA derivatives (nicogamol, lithonite and phenibut) and nicotinic acid to rats in medium therapeutic doses. Meprobamate, mebicar, and chlorodiazepoxide caused a less manifested normalizing effect of the Mg2+ -ATPase activity. It is demonstrated to be convenient to use psychotropic drugs like stress-protectors to restore/normalize the metabolism of an energy of brain neurons.
A study was performed to contrast the therapeutic effects of the racemic form of Phenibut to that of its optical isomers. The study used pharmacological tests as well as GABAB receptor binding studies to compare the effects. When locomotor activity was tested using pharmacological trials, doses of 500mg/kg, S-phenibut did not exhibit any pain or antidepressant effects but R-phenibut was observed to have a potency of about 2 times that of racemic phenibut in majority of the tests. At doses of 100mg/kg, R-phanibut was observed to significantly lower immobility time when tested in the forced swimming test. Both racemic phanibut and R-phenibut indicated analgestic activity based on the tail-flick test, but R-phenibut was particularly more active to some extent. CGP35348 (3-aminopropyl) (diethoxymethyl)phosphinic acid), a GABAB receptor-selective antagonist was observed to inhibit the antinociceptive and antidepressant effects of R-Phenibut and it also inhibited the locomotor depressing property of R-phenibut according to the open field test in vivo. During radiolingand binding experiments that employed selective GABAB receptor antagonist showed that the affinity constants for racemic phenibut, R-phenibut, and baclofen (the reference GABA-mimetic) to be 177+/-2,92+/-3, 6.0+/-1 microM, respectively. The researchers concluded that the pharmacological activity caused by racemic phenibut depended on R-phenibut, and this links to the binding affinity of the phenibut enantiomers to the GABA receptor.