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卡利拉嗪调节大鼠的睡眠结构。

Cariprazine modulates sleep architecture in rats.

机构信息

Pharmacological and Drug Safety Research, Gedeon Richter Plc, Budapest, Hungary.

出版信息

J Psychopharmacol. 2021 Mar;35(3):303-310. doi: 10.1177/0269881120981378. Epub 2021 Jan 6.

Abstract

BACKGROUND

Cariprazine is a dopamine D-preferring D/D receptor partial agonist compound recently introduced to treat schizophrenia and bipolar disorder. Although cariprazine is clinically classified as a low-somnolence drug, to date no detailed polysomnographic study is available on its effect on sleep.

AIMS

This study examined the acute systemic effects of cariprazine on the rat sleep architecture and electroencephalography spectral power.

METHODS

Sprague Dawley rats were recorded during their normal sleep period for four hours, and their sleep stages were classified.

RESULTS

Cariprazine (0.3 mg/kg i.p.) reduced the time spent in rapid eye movement (REM) sleep and increased REM latency. This dose of cariprazine decreased the gamma (40-80 Hz) band frequency oscillations and increased the theta (4-9 Hz) and alpha (9-15 Hz) frequencies during the wake periods but not during slow-wave sleep. The 0.03 mg/kg dose of cariprazine only increased the alpha power during the wake periods, while the 0.003 mg/kg dose was without any effect.

CONCLUSION

Taken together, the present results suggest that the REM-suppressing effect of cariprazine may be related to its effectiveness in improving depressive symptoms, as various drugs with similar REM-reducing properties effectively treat the depressive state, whereas the gamma power-reducing effect of cariprazine may be indicative of its efficacy in schizophrenia or mania, as similar effects have been observed with other D and 5-HT receptor antagonist drugs. These data contribute to our understanding of the complex mechanism of action that may stand behind the clinical efficacy of cariprazine.

摘要

背景

卡利拉嗪是一种多巴胺 D 受体优先 D3/D2 受体部分激动剂化合物,最近被引入用于治疗精神分裂症和双相情感障碍。尽管卡利拉嗪在临床上被归类为低镇静药物,但迄今为止,尚无关于其对睡眠影响的详细多导睡眠图研究。

目的

本研究旨在研究卡利拉嗪对大鼠睡眠结构和脑电图频谱功率的急性全身影响。

方法

在正常睡眠期间,Sprague Dawley 大鼠被记录四个小时,并对其睡眠阶段进行分类。

结果

卡利拉嗪(0.3mg/kg,ip)减少了快速眼动(REM)睡眠的时间并增加了 REM 潜伏期。该剂量的卡利拉嗪降低了觉醒期间的伽马(40-80Hz)波段频率振荡,增加了θ(4-9Hz)和α(9-15Hz)频率,但在慢波睡眠期间没有影响。卡利拉嗪 0.03mg/kg 剂量仅增加了觉醒期间的α功率,而 0.003mg/kg 剂量没有任何作用。

结论

综上所述,目前的结果表明,卡利拉嗪的 REM 抑制作用可能与其改善抑郁症状的有效性有关,因为具有类似 REM 减少特性的各种药物有效地治疗抑郁状态,而卡利拉嗪的γ功率降低作用可能表明其在精神分裂症或躁狂症中的疗效,因为其他 D 和 5-HT 受体拮抗剂药物也观察到类似的效果。这些数据有助于我们理解卡利拉嗪临床疗效背后可能存在的复杂作用机制。

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