Involvement单胺能系统中3-取代硫烷-1,1-二氧化物衍生物的抗抑郁作用

Q3 Pharmacology, Toxicology and Pharmaceutics

Research Results in Pharmacology Pub Date : 2022-06-30 DOI:10.3897/rrpharmacology.8.81007

I. Nikitina, G. G. Gaisina

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引用次数: 1

摘要

简介:本研究的目的是评估单胺能系统参与新的3-取代硫代烷-1,1-二氧化物衍生物(N-199/1)的抗抑郁作用，使用几种药理学拮抗剂和激动剂进行试验。材料和方法:我们在白色远交系雄性小鼠中进行了3组实验。在实验1中，我们评估了N-199/1在强迫游泳试验(FST)和悬尾试验(TST)中连续2周反复腹腔(i.p)给药的抗抑郁效果。在实验2中，我们评估了N-199/1与5HT1A- (WAY100635, 0.1 mg/kg)、5HT2A/2C-(酮色林，5 mg/kg)、5HT3-(昂丹西酮，1 mg/kg) 5 -羟色胺能和α - 2-肾上腺素能(育亨本，1 mg/kg)受体拮抗剂共同给药时对FST和TST的抗抑郁作用。实验3观察N-199/1对ig注射α2-肾上腺素能受体激动剂可乐定(0.3 mg/kg)致大鼠低温的影响。结果和讨论:N-199/1减少了FST中的静止时间(IT)和抑郁指数(ID)，并且在实验1中反复给药或在实验2中急性给药时对TST中的IT没有影响。在实验2中，酮色林增强了N-199/1的作用，使ID降低了36%，而WAY100635和育亨宾对其有拮抗作用，使ID和it分别比N-199/1提高27%和115%。N-199/1减弱了昂丹司琼的作用，使IT增加36%。实验中，3 N-199/1在注射可乐定1 h后降低了可乐定引起的低温。N-199/1在FST中表现出明显的抗抑郁特性，在神经药理相互作用试验中对5ht1a受体具有激动作用，对5HT2A/2C-和α2受体具有拮抗作用，这表明其抗抑郁作用机制不典型。结论:N-199/1的抗抑郁作用可能与刺激5ht1a受体，阻断5HT2A/2C-和α2受体有关。图形化的简介:

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Involvement of monoaminergic system in the antidepressant effect of 3-substituted thietane-1,1-dioxide derivative

Introduction: The aim of the study was to assess the involvement of the monoaminergic system in the antidepressant effect of a new 3-substituted thietane-1,1-dioxide derivative (N-199/1) using tests with several pharmacological antagonists and agonists. Materials and methods: We conducted 3 sets of experiments in white outbred male mice. In Experiment 1, we assessed the antidepressant effect of N-199/1 in the forced swimming test (FST) and tail suspension test (TST) when administered repeatedly for 2 weeks intraperitoneally (i.p.). In Experiment 2, we evaluated the antidepressant effect of N-199/1 in FST and TST when co-administered with 5HT1A- (WAY100635, 0.1 mg/kg), 5HT2A/2C- (ketanserin, 5 mg/kg), 5HT3- (ondansetron, 1 mg/kg) serotonergic and α2-adrenergic (yohimbine, 1 mg/kg) receptors antagonists. In Experiment 3, we assessed the effect of N-199/1 on the hypothermia induced by i.p. injection of α2-adrenergic receptors agonist clonidine (0.3 mg/kg). Results and discussion: N-199/1 reduced immobility time (IT) and index of depression (ID) in FST, and did not affect IT in TST, either when administered repeatedly in Experiment 1, or acutely in Experiment 2. In Experiment 2, ketanserin enhanced the effect of N-199/1, decreasing ID by 36%, while WAY100635 and yohimbine antagonized it, increasing ID by 27% and IT by 115%, respectively, in comparison with N-199/1. N-199/1 attenuated the effect of ondansetron, increasing IT by 36%. In Experiment, 3 N-199/1 reduced clonidine-induced hypothermia 1 h after the injection of clonidine. N-199/1 exhibited pronounced antidepressant properties in FST, an agonism to 5HT1A-receptors and an antagonism to 5HT2A/2C- and α2-receptors in tests of neuropharmacological interaction, which indicates an atypical mechanism of its antidepressant action. Conclusion: The antidepressant effect of N-199/1 is due to the stimulation of 5HT1A-receptors and blockade of 5HT2A/2C- and α2-receptors. Graphical abstract:

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