Trugman J M, Leadbetter R, Zalis M E, Burgdorf R O, Wooten G F
Department of Neurology, University of Virginia Health Sciences Center, Charlottesville 22908.
Mov Disord. 1994 Jul;9(4):441-6. doi: 10.1002/mds.870090411.
We report a patient with severe axial tardive dystonia who has had dramatic improvement for 4 years after treatment with the atypical antipsychotic drug clozapine (625 mg/day). Clozapine differs from conventional neuroleptics in that it has higher affinity for D1 and lower affinity for D2 dopamine receptors than do conventional antipsychotics, which are relatively selective D2 antagonists. We propose that repetitive stimulation of the D1 receptor by endogenous dopamine, resulting in sensitization of the D1-mediated striatal output in the presence of D2 receptor blockade, is a fundamental mechanism mediating tardive dyskinesia, including the dystonic type. According to this hypothesis, it is primarily the D1 antagonist action of clozapine that accounts for its inability to cause tardive dyskinesia as well as its therapeutic effect in tardive dystonia. Regardless of its mechanism of action, the sustained improvement observed in this case suggests that clozapine should be tried in cases of severe refractory tardive dystonia.
我们报告了一名患有严重轴性迟发性肌张力障碍的患者，在用非典型抗精神病药物氯氮平（625毫克/天）治疗后，病情显著改善达4年。氯氮平与传统抗精神病药物不同，它对D1多巴胺受体的亲和力高于传统抗精神病药物，而对D2多巴胺受体的亲和力低于传统抗精神病药物，传统抗精神病药物是相对选择性的D2拮抗剂。我们提出，内源性多巴胺对D1受体的反复刺激，在D2受体被阻断的情况下导致D1介导的纹状体输出敏感化，是介导迟发性运动障碍（包括肌张力障碍型）的一个基本机制。根据这一假设，主要是氯氮平的D1拮抗剂作用导致其不会引起迟发性运动障碍，以及其对迟发性肌张力障碍的治疗效果。无论其作用机制如何，该病例中观察到的持续改善表明，对于严重难治性迟发性肌张力障碍病例，应尝试使用氯氮平。
