Central cholinergic‐anticholinergic antagonism in Huntington's chorea
Central cholinergic‐anticholinergic antagonism in Huntington's chorea
复制标题
亨廷顿舞蹈病的中枢胆碱能-抗胆碱能拮抗作用
作者：
H. Klawans;R. Rubovits
产生亨廷顿舞蹈病的异常运动特征的生理学hlECHANIShi还没有得到很好的理解。Hasslerl、霍夫和Osler将这些多动性运动归因于病理改变的新纹状体的正常过滤机制的丧失。这一理论在细胞生物化学和生理学方面很难应用。最近，人们试图将多巴胺作为一种可能的递质与舞蹈样运动的启动联系起来。“-j多巴胺在舞蹈病产生中的意义是基于对许多药物对这种疾病的影响的观察。利血平可降低大脑中多巴胺、5-羟色胺和去甲肾上腺素的浓度，5改善亨廷顿舞蹈症的运动过度。6 -9 α-甲基-r-酪氨酸可大大降低儿茶酚胺的水平（多巴胺和去甲肾上腺素）而不影响血清素的水平，推测是通过抑制酪氨酸羟化酶的活性。该药物改善了舞蹈病性运动过度。3精神抑制剂，包括吩噻嗪类如氯丙嗪和丁酰苯类如氟哌啶醇，氯丙嗪和其他吩噻嗪类药物对舞蹈病的改善作用，9 J2 -14长期使用氟哌啶醇也能明显改善舞蹈病。15 J6降低纹状体多巴胺-利血平和α-甲基-p-酪氨酸含量的药物可改善舞蹈病。阻断多巴胺受体的药物吩噻嗪和丁酰苯也能改善舞蹈病。如果这些药物对舞蹈病的改善真的是由于减少了能够到达并作用于纹状体多巴胺受体部位的多巴胺的量，那么增加可能到达纹状体多巴胺受体的多巴胺的量应该会使舞蹈病恶化。情况似乎是这样。左旋多巴显著
THE PHYSIOLOGIC hlECHANIShi that produces the abnormal movements characteristic of Huntington's chorea is not well understood. Hasslerl and Hoff and Osler' attributed these hyperkinetic movements to a loss of the normal filter medhanisms of the pathologically altered neostriatum. This theory is difficult to apply in terms of cellular biochemistry and physiology. More recently attempts have been made to implicate dopamine as a possible transmitter in the initiation of choreiform movernents."-j The implication of dopamine in the production of chorea is based upon observations of the effects of a number of pharmacologic agents on this disease.* Reserpine, which decreases the concentration of dopamine, serotonin, and norepinephrine in the brain,5 improves the hyperkinesia of Huntington's chorea.6-9 Alpha-methyl-r-tyrosine greatly decreases the levels of catecholamines (dopamine and norepinephrine) without affecting the level of serotonin, presumably by inhibiting the activity of tyrosine hydroxylase.lO When given intravenously, this agent products improvement in choreatic hyperkinesia.3 Neuroleptics, including phenothiazines such as chlorpromazine and butyrophenones such as haloperidol, derive inuch of their central effect by blocking dopamine receptors.11 Improvement in chorea with chlorpromazine and other phenothiazines has been frequently reported.9J2-14 Definite improvement in chorea has also been demonstrated following the long-term use of haloperidol.15J6 Drugs that decrease the striatal content of dopamine-reserpine and alpha-methyl-p-tyrosine-improve chorea. Drugs that block dopamine receptors-phenothiazines and butyrophenones-also improve chorea. If the improvement in chorea seen with these agents is really due to decreasing the amount of dopamine that is able to reach and act at striatal dopamine receptor sites, then increasing the amount of dopamine that might reach the striatal dopainine receptors should worsen chorea. This appears to be the case. L-dopa markedly