N. S. Kovalev, D. A. Bakulin, L. A. Sablina, M. Yu. Vorontsov, A. S. Bykova, A. N. Reznikov, Yu. N. Klimochkin
Волгоградский государственный медицинский университет, России, Научный центр инновационных лекарственных средств; Самарский государственный технический университет, Россия, кафедра органической химии
Racemate of 3-para-tolyl-substituted GABA (tolibut) has neuroprotective, analgesic, muscle relaxant, anti-anxiety and anticonvulsant effects. The clinical application of tolibut is limited by a narrow therapeutic range. One of the ways to reduce its toxicity can be the approach of modifying the structure of GABA, in particular, replacing the amino group with a tetrazole fragment. The tetrazolyl substituent can be used as a bioisosteric analogue of various functional groups. The aim of this work is to study the anxiolytic activity of tetrazolyl derivatives of GABA with tolyl and phenyl radicals in the be- ta position. The study was performed on Wistar rats. The anxiolytic action of the (R)- and (S)-enantiomers of 3-aryl- substituted 4-(1H-tetrazol-1-yl) butanoic acids was evaluated. According to the results of the study, the presence of an- xiolytic activity in the (R) -isomer of 3-(4-methylphenyl) -4-(1H-tetrazol-1-yl) butanoic acid in a conflict situation was noted, comparable to that in tolibut and phenibut.
GABA, tolibut, phenibut, enantiomers, anxiolytic activity, rats