ANTIDEPRESSIVE EFFECT OF NEW COUMARIN DERIVATIVES

Abstract

Background: The number of patients with bipolar disorders is increasing worldwide. The search for new compounds with antidepressant activity and a low level of adverse drug reactions is an urgent task of modern psychopharmacology. Aim: To study the effect of new neuroactive coumarin derivatives on the level of depressive behavior and monoamine metabolism in the brain structures of rats Materials and methods: The antidepressant effect of the drugs LVM-091, LVM-099, LVM-S144, IEM-2886 was studied in the Porsolt forced swimming test in rats and the metabolism of monoamines in brain structures (studied by LVM-099) using high-performance liquid chromatography (HPLC). Results: Drugs LVM-091, LVM-099, LVM-S144, IEM-2886, synthesized on the basis of coumarin, decreased immobilization time in the Porsolt forced swimming test. This indicates the antidepressant effect of these substances. Administration of LVM-099 at a dose of 10 mg/kg increased homovanillic acid (HVA) level and the HVA to dopamine ratio in the nucleus accumbens. LVM-099 also increased 5-hydroxyindoleacetic acid (5-HIAA) levels and the 5-HIAA to serotonin ratio in the nucleus accumbens. In the amygdala, the level of norepinephrine, dopamine, serotonin and their metabolites did not change after administration of LVM-099. Conclusion. New coumarin derivatives cause an antidepressant effect and increase the metabolism of dopamine and serotonin in the nucleus accumbens of the rat brain, which in the future can be used in the development of new highly effective antidepressants.