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钙通道阻滞剂对小鼠的抗精神病和镇静作用。

Anti-psychotic and sedative effect of calcium channel blockers in mice.

作者信息

Umukoro S, Bakre T O, Onwuchekwa C

机构信息

Department of Pharmacology and Therapeutics, University of Ibadan, Ibadan, Nigeria.

出版信息

Afr J Med Med Sci. 2010 Dec;39 Suppl:61-6.

Abstract

Calcium channel blockers (CCBs) are widely used as therapeutic agents, for the treatment of cardiovascular disorders. However, the discovery that CCBs bind to various regions of the brain suggest that they might also offer some beneficial effects in the treatment of neuropsychiatry disorders. This study was carried out to evaluate the anti-psychotic and sedative effects of two notable calcium channel blockers, verapamil and nifedipine in mice. The anti-psychotic effects of the CCBs were studied in the animal model of amphetamine-induced stereotyped behavioral disorders. The sedative effect was assessed utilizing the prolongation of the time of sleep, induced by thiopentone. The ability of CCBs to produce catalepsy in mice was also evaluated in the study. Graded doses of verapamil (5.0-20.0 mg/kg, i.p) significantly (p<0.05) suppressed stereotyped behaviour induced by amphetamine (10.0 mg/kg, i.p). In contrast, nifedipine (5.0-20.0 mg/kg, i.p) did not exhibit anti-psychotic effect, as it could not significantly reduce stereotypy caused by amphetamine. In the test for sedation, both verapamil (5.0-20.0 mg/kg, i.p) and nifedipine (10.0-20.0 mg/kg) significantly (p<0.05) prolonged the sleeping time induced by thiopentone (50.0 mg/kg, i.p). However, neither verapamil (5.0-20.0 mg/kg, i.p.) nor nifedipine (5.0-20.0 mg/kg, i.p.) at the tested doses produced any cataleptic behaviour in the animals. The results of the study suggest that verapamil has both anti-psychotic and sedative effects without inducing the side effect of catalepsy and might be relevant in the treatment of psychosis.

摘要

钙通道阻滞剂(CCBs)作为治疗药物被广泛用于治疗心血管疾病。然而,有发现表明CCBs可与大脑的不同区域结合,这提示它们在治疗神经精神疾病方面可能也具有一些有益作用。本研究旨在评估两种著名的钙通道阻滞剂维拉帕米和硝苯地平对小鼠的抗精神病和镇静作用。在苯丙胺诱导的刻板行为障碍动物模型中研究了CCBs的抗精神病作用。利用硫喷妥钠诱导睡眠的时间延长来评估镇静作用。本研究还评估了CCBs在小鼠中产生僵住症的能力。维拉帕米(5.0 - 20.0毫克/千克,腹腔注射)的分级剂量显著(p<0.05)抑制了由苯丙胺(10.0毫克/千克,腹腔注射)诱导的刻板行为。相比之下,硝苯地平(5.0 - 20.0毫克/千克,腹腔注射)未表现出抗精神病作用,因为它不能显著减少由苯丙胺引起的刻板行为。在镇静试验中,维拉帕米(5.0 - 20.0毫克/千克,腹腔注射)和硝苯地平(10.0 - 20.0毫克/千克)均显著(p<0.05)延长了由硫喷妥钠(50.0毫克/千克,腹腔注射)诱导的睡眠时间。然而,在所测试剂量下,维拉帕米(5.0 - 20.0毫克/千克,腹腔注射)和硝苯地平(5.0 - 20.0毫克/千克,腹腔注射)均未在动物中产生任何僵住症行为。该研究结果表明,维拉帕米具有抗精神病和镇静作用,且不会诱发僵住症的副作用,可能与精神病的治疗相关。

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