Richter A, Löscher W
Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, Hannover, Germany.
Eur J Pharmacol. 1993 Oct 5;242(3):309-12. doi: 10.1016/0014-2999(93)90256-h.
The effects of the atypical neuroleptic clozapine were studied in an inbred line of Syrian golden hamsters with generalized dystonia, i.e. a frequent movement disorder in humans. The effects of clozapine were compared with those of the classical neuroleptic, haloperidol. Clozapine, 7.5-20 mg/kg i.p., potently reduced the severity of dystonic attacks in the mutant hamster model, but induced marked sedation at these doses. Lower doses were ineffective. Haloperidol, 0.5 mg/kg i.p., significantly reduced the severity of dystonia without marked sedation. The finding that clozapine possesses antidystonic potency similar to that of haloperidol in a genetic model of dystonia might suggest that this atypical neuroleptic is an effective alternative in the treatment of dystonic patients who respond to neuroleptics, particularly because of the clinical evidence that clozapine is almost devoid of extrapyramidal adverse effects.
在患有全身性肌张力障碍(一种在人类中常见的运动障碍)的近交系叙利亚金仓鼠中研究了非典型抗精神病药物氯氮平的作用。将氯氮平的作用与经典抗精神病药物氟哌啶醇的作用进行了比较。腹腔注射7.5 - 20mg/kg的氯氮平能有效降低突变仓鼠模型中肌张力障碍发作的严重程度,但在这些剂量下会引起明显的镇静作用。较低剂量无效。腹腔注射0.5mg/kg的氟哌啶醇能显著降低肌张力障碍的严重程度,且无明显镇静作用。在肌张力障碍的遗传模型中,氯氮平具有与氟哌啶醇相似的抗肌张力障碍效力,这一发现可能表明,这种非典型抗精神病药物是治疗对抗精神病药物有反应的肌张力障碍患者的有效替代药物,特别是因为有临床证据表明氯氮平几乎没有锥体外系不良反应。