Therapeutic potential of α2 adrenoceptor antagonism for antipsychotic-induced extrapyramidal motor disorders
Therapeutic potential of α2 adrenoceptor antagonism for antipsychotic-induced extrapyramidal motor disorders
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DOI：
10.1016/j.neulet.2009.03.001
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发表时间：
2009-04-24
影响因子：
2.5
通讯作者：
Ohno, Yukihiro
中科院分区：
文献类型：
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作者：
Imaki, Junta;Mae, Yukari;Ohno, Yukihiro
我们研究了JP-1302（一种选择性α（2C）拮抗剂）、BRL-44408（一种选择性α（2A）拮抗剂）和育亨宾（一种非选择性α（2）拮抗剂）对氟哌啶醇诱导的小鼠运动迟缓和僵住症的影响，以阐明α（2）肾上腺素受体亚型在改善锥体外系运动障碍中的作用。JP-1302（0.1-1 mg/kg，s.c.）剂量依赖性地改善氟哌啶醇诱导的运动迟缓在杆测试和逆转僵硬时间增加氟哌啶醇。JP-1302的抗运动迟缓和抗惊厥作用在0.3和1 mg/kg时具有统计学显著性，并且这些剂量在旷场试验中未改变走动距离、直立或中心-周边停留时间。BRL-44408（1-10 mg/kg，s.c.）和育亨宾（0.3-3 mg/kg，i. p.）还改善氟哌啶醇诱导的运动迟缓和僵住症。然而，在旷场试验中，两种药物均显著减少了步行距离和直立，可能反映了与α 2拮抗作用相关的焦虑作用。本研究首次表明，α（2C）受体阻滞剂可以减轻抗精神病药诱导的锥体外系运动障碍，而不影响粗行为。(C)2009爱思唯尔爱尔兰有限公司保留所有权利。
We examined the effects of JP-1302 (a selective alpha(2C) antagonist), BRL-44408 (a selective alpha(2A) antagonist) and yohimbine (a non-selective alpha(2) antagonist) on haloperidol-induced bradykinesia and catalepsy in mice to elucidate the role of alpha(2) adrenoceptor subtypes in modifying extrapyramidal motor disorders. JP-1302 (0.1-1 mg/kg, s.c.) dose-dependently ameliorated haloperidol-induced bradykinesia in the pole-test and reversed the catalepsy time increased by haloperidol. Antibradykinetic and anticataleptic actions of JP-1302 were statistically significant at 0.3 and 1 mg/kg, and these doses did not alter the ambulatory distance, rearing or center-perimeter residence time in the open-field test. BRL-44408 (1-10 mg/kg, s.c.) and yohimbine (0.3-3 mg/kg, i.p.) also ameliorated haloperidol-induced bradykinesia and catalepsy. However, both agents significantly decreased ambulatory distance and rearing in the open-field test, possibly reflecting their anxiogenic actions associated with alpha(2) antagonism. The present study shows for the first time that blockade of alpha(2C) receptors can alleviate antipsychotic-induced extrapyramidal motor disorders without affecting gross behaviors. (C) 2009 Elsevier Ireland Ltd. All rights reserved.