PHARMACOLOGICAL EVALUATION OF THE SPECTRUM OF PSYCHOTROPIC ACTIVITY OF NEW SYNTHESIZED DERIVATIVES IF 4-OXOPYRIMIDINE AND AMIDES OF ORTO-BENZOYL AMINOBENZOIC ACID, PREDECESSORS OF QUINAZOLINE-4

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Purpose of the work: the estimation of spectrum of psychotropic activity of biologically active compounds - derivatives of 4-oxo-pyramidine and amids of orto-benzoyl aminobenzoic acid, predecessors of quinazoline-4. Materials and methods of the study: we have studied 14 excipients: derivatives of 4-oxopyrimidine and amides of orto-benzoyl aminobenzoic acid, derivatives of predecessors of quinazolinone-4 (synthesized at the Department of Organic Chemistry at Pyatigorsk Medical and Pharmaceutical Institute under the direction of Ph.D. in Pharmacy, Professor E.T. Oganesyan, Ph.D. in Pharmacy I.P. Kodonidi). Experimental animals were 969 reproductive white Wistar rats weighed 220-250 g. We studied the substances in conditions of conflict situations, elevated plus maze, open field, multiparametric testing, forced swimming at doses 25, 50, 75 mg\kg in abdominal injection in evenings. Diazepam tranquilizer, amitriptyline antidepressants, fluoxetine were the comparative drugs. A group of male rats, which were given 0.4 ml of tween-80 solution or physiological solution (control group for diazepam, antidepressants) abdominally, were the control group in every series of the runs for each method for the estimation of the activity under study. The data obtained are processed with a statistic package of standard computer programs with the estimation of normality of the distribution on Shapiro-Wilk W-statistics. Statistically significant parametrical differences were revealed by using Student’s criterion, non-parametric criteria of Kruskal-Wallis, Mann-Whitney, Wilcoxon. Differences with p<0.05 were considered statistically significant for all types of analysis. Results: following the results of male rats testing in the conditions of conflict situation we have revealed leader-compounds - derivatives of 4-oxopyrimidine (III, V, VII) and amides of orto-benzoyl aminobenzoic acid, predecessors of quinazoline-4 (XII-XIV), which exhibit the strongest anticonflict action. Apart from that, latence of the first access to a feeding bowl limited due to the substances studied. Derivatives of 4-oxopyrimidine and amides of orto-benzoyl-aminobenzoic acid, predecessors of quinazolinone-4 manifested an antianxiolitic action on the elevated plus maze (EPM), increasing a number of visits during the presence of male rats in light arms, decreasing a latent period of the presence in dark arms of EPM. Limiting effect of the excipients under study on the emotional reactivity of the animals was proved in the conditions of an “open field” and multiparametric testing in one-time and chronic (14 days) injection. It revealed separation of an anxiolytic effect, accompanied with sedative and or activating action for certain substances. While evaluating the swimming behavior of animals we have revealed an increased time of active and decrease of passive swimming, decrease of depressiveness index, change of biorhythmic pattern of swimming, which allowed stating the presence of antidepressant activity of the derivatives of 4-oxopyrimidine (III, V, VII) and predecessors of quinazoline-4 (XII-XIV). Conclusions: thus, we have established the leader-compounds among the studied substances - derivatives of 4-oxopyrimidine and amides of orto-benzoyl aminobenzoic acid, predecessors of quinazoline-4, which have a significant anxiolytic effects. We have revealed antiamnestic, activating, antidepressant action of leader-compounds.