Barbeau A
Can Med Assoc J. 1969 Dec 27;101(13):59-68.
The last 10 years have seen great activity in the investigation of cerebral catecholamines, particular attention having been paid to dopamine. The low dopamine content in the basal ganglia and in the urine of patients with Parkinson's disease led to the logical use of the precursor DOPA in the treatment of this disorder. Between 1961 and 1966, both the oral and the intravenous routes were utilized and some effects were noted upon akinesia and rigidity. The doses then used were low and the results remained somewhat controversial. When higher oral levels of L-dopa were introduced, the beneficial action of L-dopa upon parkinsonian symptoms and signs was proved beyond doubt, but there came to light a number of troublesome side effects, the worst of which were hypotension and a variety of abnormal involuntary movements. Recently, new approaches to the therapy have been tried and the sum total of these observations is to challenge our peace of mind regarding a seemingly logical chain of events. We are convinced that such second thoughts will eventually result in better and safer methods of treating this too frequent and disabling neurological disorder.
在过去十年中,对脑内儿茶酚胺的研究十分活跃,其中多巴胺受到了特别关注。帕金森病患者基底神经节和尿液中的多巴胺含量较低,这使得前体多巴在治疗该疾病中的应用成为合理选择。1961年至1966年间,人们采用了口服和静脉注射两种给药途径,并观察到对运动不能和强直有一定效果。当时使用的剂量较低,结果仍存在一定争议。当引入更高口服剂量的左旋多巴时,左旋多巴对帕金森病症状和体征的有益作用得到了确凿证明,但同时也出现了一些麻烦的副作用,其中最严重的是低血压和各种异常的不自主运动。最近,人们尝试了新的治疗方法,这些观察结果的总和让我们对这一看似合理的事件链的安心感受到了挑战。我们相信,这样的重新思考最终将带来更好、更安全的方法来治疗这种常见且致残的神经系统疾病。