The mechanism of antidepressant action of a new 3-substituted thiethane-1,1-dioxide derivative in tests of neuropharmacological interaction

Авторы

DOI:

https://doi.org/10.3897/rrpharmacology.8.86560

Аннотация

Introduction: The present study is aimed at investigation of the mechanism of action of a new 3-substituted thi­etane-1,1-dioxide derivative (N-199/1) exhibiting antidepressant properties, in several tests of neuropharmaco­logical interaction.

Materials and methods: To study the mechanism of action of N-199/1, its effect on 5-hydroxytryptophan (5-HTP)-induced head-twitch response (50 mg/kg and 300 mg/kg), haloperidol-induced catalepsy (1 mg/kg), arecoline-induced tremor (6 mg/kg), picrotoxin-induced seizures (6 mg/kg) and hypothermia, induced by apomorphine (10 mg/kg) or L-3,4-dihydroxyphenylalanine (L-DOPA, 140 mg/kg), was assessed when administered singly to white outbred male mice at a dose of 2 mg/kg.

Results and discussion: N-199/1 reduced the number of head twitches, induced by 5-HTP (300 mg/kg), by 83% 45 min after 5-HTP injection; decreased the duration of haloperidol catalepsy by 1–32 s 15–45 min after haloperidol injection; attenuated L-DOPA-induced hypothermia by 0.7 °С and apomorphine-induced hypothermia by 0.6 °С at the timepoint of 30 min; reduced the duration and severity of arecoline tremor and did not affect the convulsive effect of picrotoxin.

Conclusion: N-199/1 acts on serotonergic, noradrenergic, dopaminergic and cholinergic neurotransmission and does not affect neuronal reuptake of monoamines or monoamine oxidase. The mechanism of action of N-199/1 is probably due to stimulation of serotonergic 5HT1A-receptors and/or blockade of 5HT2A/2C-receptors and/or α2-adrenergic receptors; dopaminergic and cholinergic receptors may also be involved.

Graphical abstract:

Ключевые слова:

5-hydroxytryptophan, animal outbred strain, antidepressants, apomorphine, arecoline, haloperidol, L-DOPA, thietane

Вклад авторов

Irina L. Nikitina, Bashkir State Medical University

Doctor of Sciences, Professor of Department of Pharmacology with a course of Clinical Pharmacology.

Gulnara G. Gaisina, Bashkir State Medical University

Post-graduate student, Assistant of Department of Pharmacology with a course of Clinical Pharmacology.

Aleksandr V. Samorodov, Bashkir State Medical University

Doctor of Sciences, Head of Department of Pharmacology with a course of Clinical Pharmacology.

Загрузки

Опубликован

22.12.2022

Как цитировать

Nikitina IL, Gaisina GG, Samorodov AV (2022) The mechanism of antidepressant action of a new 3-substituted thiethane-1,1-dioxide derivative in tests of neuropharmacological interaction. Research Results in Pharmacology 8(4): 175–183. https://doi.org/10.3897/rrpharmacology.8.86560

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Обзорная статья