Stafford J R, Fann W E
Dis Nerv Syst. 1977 Dec;38(12 Pt 2):3-6.
A total of twenty-nine patients have thus far been treated with deanol in various dosage levels for periods ranging from five to thirty days. Clinical response has been pronounced, even dramatic, in seven patients, moderate but significant in nine patients, and slight to insignificant in thirteen others. Videotape rating and quantitative accelerometry, to the extent that they constitute novel and stress-inducing experiences may not be representative of global clinical changes. Deanol did not produce the anticipated elevation in choline levels postulated to be one mechanism of its action. The failure of deanol to achieve this effect may most probably be attributed to interval after last dose, to inadequate level of deanol or to some alteration in choline metabolism in the presence of deanol. The etiology of tardive dyskinesia at biochemical and structural levels is complex. For some patients improvement has been dramatic and clearly associated with deanol. Others appear to exhibit minimal response which cannot be differentiated from placebo or environmental effects. Our present strategy, in common with that of other authors includes the administration of a "challenge" dose of rapid acting injectable cholinomimetic agents (e.g. physostigmine) and dopamine-blocking agents (e.g. haloperidol) with placebo controls. In this manner therapy may be more rationally selected for long-term use and may logically include deanol. The correlation of such predictive challenges with response to long-term treatment is an area for much more well controlled study.
截至目前,共有29名患者接受了不同剂量的二甲基乙醇胺治疗,治疗时间从5天到30天不等。7名患者的临床反应显著,甚至非常明显;9名患者的反应中等但有意义;另外13名患者的反应轻微或无意义。录像评分和定量加速度测量,就其构成新颖且诱发压力的体验而言,可能无法代表整体临床变化。二甲基乙醇胺并未产生预期的胆碱水平升高,而这被认为是其作用机制之一。二甲基乙醇胺未能达到这一效果,很可能归因于最后一剂后的间隔时间、二甲基乙醇胺水平不足或在二甲基乙醇胺存在的情况下胆碱代谢的某些改变。迟发性运动障碍在生化和结构层面的病因很复杂。对一些患者来说,改善非常明显,且显然与二甲基乙醇胺有关。另一些患者似乎反应极小,无法与安慰剂或环境影响区分开来。我们目前的策略与其他作者的策略一样,包括给予“激发”剂量的快速起效的拟胆碱药物(如毒扁豆碱)和多巴胺阻断剂(如氟哌啶醇),并设置安慰剂对照。通过这种方式,可以更合理地选择长期使用的治疗方法,并且合理地可能包括二甲基乙醇胺。这种预测性激发与长期治疗反应之间的相关性是一个需要更严格对照研究的领域。