Denney D, Stevens J R
Department of Psychiatry, Oregon Health Sciences University, Portland 97201, USA.
Biol Psychiatry. 1995 Apr 1;37(7):427-33. doi: 10.1016/0006-3223(94)00237-W.
Epileptiform EEG changes, myoclonus, and seizures are reported in some patients treated with clozapine. Although these are undesirable side effects, the excitation of specific neuronal networks by clozapine and other neuroleptics may be important for the therapeutic effect of this class of agents. In these experiments, intraperitoneal clozapine 2-16 mg/kg produced dose-related myoclonic jerks in partially restrained rats. Paroxysmal slow waves and spike activity were recorded from implanted electrodes in amygdala, hippocampus, and cortex following higher doses of clozapine, but the EEG abnormalities were not correlated with the myoclonic jerks. Single doses of chlorpromazine (8 and 16 mg/kg) rarely produced myoclonic jerks but provoked generalized tonic seizures in two animals preceded by multiple myoclonic jerks in one. Myoclonus and seizures reflect increased excitability of the central nervous system. It is possible that clozapine and other neuroleptics exert a therapeutic effect by increasing excitability in critical subcortical areas of the brain.
据报道，一些使用氯氮平治疗的患者会出现癫痫样脑电图改变、肌阵挛和癫痫发作。尽管这些是不良副作用，但氯氮平和其他抗精神病药物对特定神经网络的兴奋作用可能对这类药物的治疗效果很重要。在这些实验中，腹腔注射2 - 16毫克/千克的氯氮平会在部分受限的大鼠中产生剂量相关的肌阵挛性抽搐。在给予较高剂量的氯氮平后，从植入杏仁核、海马体和皮层的电极记录到阵发性慢波和棘波活动，但脑电图异常与肌阵挛性抽搐并无关联。单次剂量的氯丙嗪（8和16毫克/千克）很少产生肌阵挛性抽搐，但在两只动物中引发了全身性强直发作，其中一只在发作前出现了多次肌阵挛性抽搐。肌阵挛和癫痫发作反映了中枢神经系统兴奋性的增加。氯氮平和其他抗精神病药物有可能通过增加大脑关键皮层下区域的兴奋性来发挥治疗作用。
