The dynamics of the antidepressant effect of atristamine in the repeated dose study
Keywords:2-methyl-3-(phenylaminomethyl)-1H-quinolin-4-one, atristamine, antidepressant effect, tail suspension test, repeated dose study
Taking into account the peculiarities of the clinical application of antidepressants, namely gradual development of a therapeutically significant effect and a considerable duration of courses of treatment, an important aspect of the experimental study of promising antidepressants is the study of their antidepressant effect in the dynamics in the repeated dose studies.
Aim. To study experimentally the dynamics of the antidepressant effect of a promising antidepressant atristamine using the repeated dose design of the experiment.
Materials and methods. The tail suspension test was chosen in order to study the dynamics of development of the atristamine antidepressant effect. Atristamine (100 mg/kg/day) and isotonic solution (control group) was injected for 14 days. The studies of depressive behaviour of animals were performed on days 1, 4, 7, 10 and 14 of the experiment.
Results. The total immobility time of mice, which in the tail suspension test was the main marker of the antidepressant activity, in the group of atristamine was practically the same as that in the intact control group on the first day of the study (1 hour after single administration). On day 4 of the study, the total immobility time of the animals in the atristamine group was significantly shorter (–26.9 %) than in the intact control group. The latency to the first immobility episode of animals receiving atristamine compared to those of the intact control group was 77 % longer. On day 7 of the study, the immobility time of the atristamine group animals was shorter by 30.2 %, the latency to the first immobility episode increased by 88.2 %, and the average duration of one episode of immobility reduced by 43.5 %. On days 10 and 14 of the experiment, the results of the tail suspension test in the atristamine group confirmed further enhancement of the antidepressant effect of the test compound. The antidepressant activity was 38.4 % and 37.7 %, respectively.Conclusions. There were no significant changes in the main markers of the antidepressant effect in the group of animals receiving atristamine after single administration. This fact can be explained by the effects of pharmacokinetic or pharmacogenetic factors. The analysis of the results in the subsequent periods of the experiment showed that the antidepressant effect of atristamine reached a reliable level on day 4 and continued to increase, on day 7 it achieved the maximum level by all markers of the tail suspension test and remained at this level to the end of the experiment.
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