Lutsenko R. Pharmacological properties of new 2-oksoindoline-3-glyoxylic acid derivatives as prospective neurotropic drugs

New derivatives of 2-oxoindolin-3-glyoxylic acid with neuropsychotropic action were theoretically and experimentally investigated, and pharmacological peculiarities and mechanisms of action of the leader compound (substance 18) between these potential neuropsychotropic agents were determined. A screening study based on the results of computer programs PASS and GUSAR detected that they are low-toxic, possess neurotropic (anxiolytic, anticonvulsant, hypnotic, nootropic, etc.), antihypoxic, anti-inflammatory, antitumor, antiviral actions, influence 5-HT, GABA-, NMDA- and ANMP-receptors and inhibit GABA-aminotransferase. Changes in rats’ emotional and behavioral reactions in specific ethological tests for the presence of anxiolytic properties were analyzed. According to the results of a linear discriminant analysis of emotional and behavioral reactions, it was identified a leader compound that approximated indices of animals to favorable effect during diazepam intake. It was found that 2-hydroxy-N-naphthalen-1-yl-2- (2-oxo-1,2-dihydro-indol-3-ylidene)-acetamide (laboratory code 18) when it was administered intraperitoneally to mice at LD50 (3250±159 mg/kg) belongs to relatively harmless substances (VI class of toxicity) and its toxicity in 88 times is lower than the same of diazepam. When it was administered intraperitoneally to rats, the ED50 was 11.9±2.85 mg/kg and therapeutic index of the compound 18 was 14.8 times higher than the same of diazepam. Compound 18 can be proposed for further clinical experiments as a new safe agent for the treatment of neurotic, stress-related and somatoform disorders, including social anxiety, panic disorder, generalized anxious disorder, mixed anxiety-depressive disorder, and post-traumatic stress disorder. (emotional lability, memory impairment, decreased concentration and attention), anxiety, fear, obsessive-compulsive disorder, as well as for the prevention of stress, especially against the background of heart and liver problems