Davis K L, Berger P A
Biol Psychiatry. 1978 Feb;13(1):23-49.
The hypotheses of relative cholinergic underactivity in Huntington's disease, tardive dyskinesia, mania, and schizophrenia were pharmacologically investigated, using physostigmine and choline chloride. Intravenous physostigmine improved the involuntary movements of all of four patients with tardive dyskinesia and three of six patients with Huntington's disease. Physostigmine infusion also decreased manic symptoms in six of nine patients with mania, but had no beneficial effects in three patients with schizophrenia. Precursorloading with choline chloride may increase brain acetylcholine levels and central cholinergic activity. In patients with movement disorders a transient improvement during physostigmine infusion predicted a positive response to a trial of oral choline chloride. One manic patient may have been improved by choline chloride, however choline chloride did not improve symptoms in four of six schizophrenix patients. Chronic treatment with oral choline chloride increases plasma levels of choline during administration and for approximately 48 hr after discontinuation of treatment. A single 5-g dose of choline chloride also transiently raises plasma choline levels. These results with physostigmine support the hypotheses of cholinergic underactivity in Huntington's disease, tardive dyskinesia, and mania. Agents which might chronically increase cholinergic activity such as choline chloride should be further tested in these disorders.
使用毒扁豆碱和氯化胆碱，对亨廷顿舞蹈病、迟发性运动障碍、躁狂症和精神分裂症中胆碱能相对活性不足的假说进行了药理学研究。静脉注射毒扁豆碱改善了4例迟发性运动障碍患者中的所有患者以及6例亨廷顿舞蹈病患者中的3例的不自主运动。毒扁豆碱输注还减轻了9例躁狂症患者中6例的躁狂症状，但对3例精神分裂症患者没有有益影响。用氯化胆碱进行前体负荷可能会增加脑内乙酰胆碱水平和中枢胆碱能活性。在患有运动障碍的患者中，毒扁豆碱输注期间的短暂改善预示着对口服氯化胆碱试验的阳性反应。1例躁狂症患者可能因氯化胆碱而病情改善，然而，氯化胆碱并未改善6例精神分裂症患者中4例的症状。口服氯化胆碱的长期治疗在给药期间以及停药后约48小时内会增加血浆胆碱水平。单次5克剂量的氯化胆碱也会使血浆胆碱水平短暂升高。这些毒扁豆碱的结果支持了亨廷顿舞蹈病、迟发性运动障碍和躁狂症中胆碱能活性不足的假说。可能会长期增加胆碱能活性的药物，如氯化胆碱，应在这些疾病中进一步进行测试。
