Antidepressant effect of new coumarin derivatives

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Abstract

BACKGROUND: The incidence of bipolar disorder is increasing worldwide. The search for new compounds with antidepressant activity and milder adverse drug reactions is an urgent task of modern psychopharmacology.

AIM: This study aimed to analyze 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 effects of LVM-091, LVM-099, LVM-S144, and IEM-2886 were evaluated in rats subjected to the Porsolt forced swimming test and the metabolism of monoamines in brain structures (LVM-099) using high-performance liquid chromatography.

RESULTS: LVM-091, LVM-099, LVM-S144, and IEM-2886, synthesized from coumarin, decreased the immobilization time of the experimental rats in the Porsolt forced swimming test, indicating the antidepressant effect of these substances. The administration of LVM-099 at a dose of 10 mg/kg increased the level of homovanillic acid and the homovanillic acid-to-dopamine ratio in the nucleus accumbens. LVM-099 also increased 5-hydroxyindoleacetic acid levels and the 5-hydroxyindoleacetic acid-to-serotonin ratio in the nucleus accumbens. In the amygdala, the levels of norepinephrine, dopamine, serotonin, and their metabolites did not change after LVM-099 administration.

CONCLUSIONS: New coumarin derivatives exert antidepressant effects and increase the metabolism of dopamine and serotonin in rat nucleus accumbens, which can be used in the development of new highly effective antidepressants.

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About the authors

Bakhodir B. Daliev

Institute of Experimental Medicine

Author for correspondence.
Email: bahodirdaliev@gmail.com
ORCID iD: 0000-0001-5966-8783
Russian Federation, Saint Petersburg

Dmitrii I. Klimenko

Institute of Experimental Medicine

Email: dima.klimenko999@mail.ru
ORCID iD: 0009-0007-8168-7228
SPIN-code: 8481-4489
Russian Federation, Saint Petersburg

Inessa V. Karpova

Institute of Experimental Medicine

Email: inessa.karpova@gmail.com
ORCID iD: 0000-0001-8725-8095
SPIN-code: 9874-4082

Dr. Sci. (Biology), Assistant Professor

Russian Federation, Saint Petersburg

Leonid V. Myznikov

Institute of Experimental Medicine

Email: myznikov_lv@mail.ru
ORCID iD: 0000-0002-0863-3027

Dr. Sci. (Chemistry), Assistant Professor

Russian Federation, Saint Petersburg

Evgenii R. Bychkov

Institute of Experimental Medicine

Email: bychkov@mail.ru
ORCID iD: 0000-0002-8911-6805
SPIN-code: 9408-0799

Dr. Sci. (Medicine)

Russian Federation, Saint Petersburg

Andrey A. Lebedev

Institute of Experimental Medicine

Email: aalebedev-iem@rambler.ru
ORCID iD: 0000-0003-0297-0425
SPIN-code: 4998-5204

Dr. Sci. (Biology)

Russian Federation, Saint Petersburg

Petr D. Shabanov

Institute of Experimental Medicine

Email: pdshabanov@mail.ru
ORCID iD: 0000-0003-1464-1127
SPIN-code: 8974-7477

Dr. Sci. (Medicine), Professor

Russian Federation, Saint Petersburg

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