B-193

A potential antidepressant activity of B-193 was studied in mice and rats. In in vitro studies B-193 did not affect the uptake of NA and 5-HT. In in vivo models the tested compound did not influence the reserpine-induced hypothermia, hypoactivity and ptosis, the stimulating action of L-DOPA, the apomorphine-induced hypothermia. On the other hand, it produced a positive effect in the despair test. When given repeatedly, it evoked adaptive changes in brain neurotransmitter receptors, i.e. it decreased the density of beta-adrenoceptors and increased the number of alpha 1 ones; those changes were accompanied with functional alternations in the reactivity of those receptors: an attenuated behavioral reaction to salbutamol and enhanced aggressiveness induced by a high dose of clonidine. Furthermore, B-193 administered repeatedly enhanced hyperlocomotion induced by amphetamine but did not influence the stereotypy induced by apomorphine. These results indicate that B-193 possesses properties characteristic for atypical antidepressants.

The cumulative, subchronic and chronic toxicity of B-193 were studied on the rats and mice. It was found that this compound exerted weak tendency to cumulation in the body. Only the highest doses of B-193 (70, 40 mg/kg po for 12 weeks) caused the increase of animals mortality. Studies on subchronic and chronic toxicity have demonstrated, that B-193 administrated po or ip for 3 weeks, and po for 12 weeks, in general, neither affects the body weight gain nor the mass and morphology of heart, liver and kidneys, as well as spontaneous locomotor activity of animals. The weak depressant effect of B-193 on peripheral blood morphology was seen only after 3 weeks po or ip treatment with this compound. The moderate effect of B-193 on activity of alanine and aspartate transaminases (A1At and AspAt) and serum protein level found after 3 weeks of treatment, was no longer observed after 12 weeks of treatment. This could indicate that above effects of B-193 are reversible.