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氟伏沙明精神药理学特征的临床前证据。

Preclinical evidence on the psychotropic profile of fluvoxamine.

作者信息

Olivier B, Bosch L, van Hest A, van der Heyden J, Mos J, van der Poel G, Schipper J, Tulp M

机构信息

Solvay Duphar B. V., Weesp, The Netherlands.

出版信息

Pharmacopsychiatry. 1993 May;26 Suppl 1:2-9. doi: 10.1055/s-2007-1014370.

Abstract

Serotonin (5-HT) reuptake inhibitors (SSRIs) such as fluvoxamine are interesting compounds. Initially launched as antidepressants, they have been found to be active in various psychiatric disorders besides depression, including obsessive-compulsive disorder, panic disorder, and eating disturbances. Preliminary data suggest their efficacy in alcohol and drug abuse, aggression, and posttraumatic stress disorder as well. Along with those clinical findings, new preclinical data have emerged. For example, fluvoxamine has demonstrated activity in various models of anxiety in rodents. Its anxiolytic activity can be clearly discriminated from that of the benzodiazepines. In the DRL 72-sec paradigm, fluvoxamine exhibits a good antidepressant profile, similar to those of imipramine and flesinoxan. Studies have shown that fluvoxamine does not down-regulate beta-adrenoceptors; apparently, that property is not a conditio sine qua non for antidepressant activity. Results of studies of the mechanism of action of fluvoxamine in which drug discrimination tests were performed with rats and pigeons suggest that the fluvoxamine stimulus is not (or is only to a very limited degree) dependent on activation of 5-HT1A receptors or 5-HT1B/1D receptors, or both. Experimentation is ongoing in those animal models.

摘要

氟伏沙明等5-羟色胺(5-HT)再摄取抑制剂是一类有趣的化合物。它们最初作为抗抑郁药推出,现已发现除抑郁症外,在包括强迫症、恐慌症和饮食失调在内的各种精神疾病中也有活性。初步数据表明它们在酒精和药物滥用、攻击行为以及创伤后应激障碍方面也有疗效。随着这些临床发现,新的临床前数据也已出现。例如,氟伏沙明在啮齿动物的各种焦虑模型中已显示出活性。其抗焦虑活性可明显区别于苯二氮䓬类药物。在DRL 72秒范式中,氟伏沙明表现出良好的抗抑郁特征,类似于丙咪嗪和氟西诺生。研究表明氟伏沙明不会下调β-肾上腺素能受体;显然,该特性并非抗抑郁活性的必要条件。对氟伏沙明作用机制进行的研究(其中对大鼠和鸽子进行了药物辨别试验)结果表明,氟伏沙明刺激并非(或仅在非常有限的程度上)依赖于5-HT1A受体或5-HT1B/1D受体或两者的激活。在这些动物模型中的实验正在进行。

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