Sertindole 5 -羟色胺5-HT2c反向激动剂,减少但不是5-HT2c受体拮抗剂绑定后慢性治疗。

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Hietala J, Kuonnamaki M, Palvimaki EP, Laakso, Majasuo H, Syvalahti E

Sertindole 5 -羟色胺5-HT2c反向激动剂,减少但不是5-HT2c受体拮抗剂绑定后慢性治疗。

精神药理学(Berl)。2001年9月,157 (2):180 - 7。

PubMed ID

11594443 (在PubMed

]

文摘

理由是:Sertindole是一种新型抗精神病药物具有高亲和力的多巴胺D2, alpha-1-adrenoceptors和5 -羟色胺5-HT2A 5-HT2c受体。sertindole 5-HT2c受体组成部分可能是临床相关监管这种受体亚型有牵连的焦虑、认知/记忆和大脑可塑性。目的:描述交互的sertindole 5-HT2C受体使用老鼠脉络丛作为生理受体来源。结果:Sertindole摩尔5-HT2c体外受体的亲和力。Sertindole得罪5-HT-stimulated磷酸肌醇(PI)水解,如氯氮平,也抑制基底π水解表明Sertindole 5-HT2C受体反兴奋剂。重复sertindole剂量对5-HT2C受体的影响研究在大鼠治疗21天sertindole(300和1250年microg /公斤/天)。氯氮平(25毫克/公斤/天)作为对照药物。5-HT2C受体结合在脉络丛测量拮抗剂和激动剂配体([3 h] mesulergine和[125 i] DOI)使用定量放射自显影法撤军后8天。氯氮平5-HT2C受体拮抗剂和激动剂结合位点同样降低了36%和32%,分别。Sertindole没有引起重大变化的总数5-HT2C受体,但最高剂量的Sertindole降低[3 h]的亲和力mesulergine 5-HT2C受体。 This was most likely due to residual sertindole levels in the brain which was supported by direct concentration measurements. In contrast, sertindole induced a highly significant and dose-related decrease in 5-HT2C agonist binding (up to 77%). Neither drug affected striatal D2 receptor binding. CONCLUSIONS: Sertindole, like clozapine, was found to be a serotonin 5-HT2C receptor inverse agonist. The preferential downregulation of 5-HT2C receptor agonist (G-protein-coupled) sites by chronic administration seemed to differentiate sertindole from clozapine at these dose regimens. The 5-HT2c receptor downregulation during repeated dosing may contribute to therapeutic efficacy and/or side effects of sertindole treatment.

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药物靶点

药物	目标	类	生物	药理作用	行动
Sertindole	5 -羟色胺受体2	蛋白质	人类	是的	拮抗剂	细节
Sertindole	5 -羟色胺受体2摄氏度	蛋白质	人类	是的	拮抗剂	细节
Sertindole	Alpha-1A肾上腺素能受体	蛋白质	人类	未知的	不可用	细节