Jann M W, Froemming J H, Borison R L
Department of Pharmacy Practice, Mercer University, Atlanta, GA 30312.
J Am Board Fam Pract. 1990 Apr-Jun;3(2):111-9.
Dopamine is a neurotransmitter affecting motor function, and the dopamine system is the focus of abnormality in dyskinetic diseases. An important side effect of many psychotropic drugs possessing dopamine activity is the production of movement disorders; this potential problem needs to be examined carefully with any new central nervous system drug, such as the azapirone anxiolytic drugs. The pharmacology of the azapirones, represented by the prototype, buspirone, involves several different neuroreceptor systems. Current evidence indicates that buspirone's anxiolytic activity is mediated through serotonergic mechanisms. It also displays some binding affinity for dopamine receptors, which necessitates comparisons between buspirone and neuroleptic agents in preclinical tests, clinical studies, and case reports. Although similarities occurred in some biochemical studies, neuroleptics, and not buspirone, caused an increase in dopamine receptors with chronic use. Neuroleptics typically produce this change after long-term use, which is thought to be a key factor leading to tardive dyskinesia. In standard animal behavior studies, buspirone's profile failed to match neuroleptic agents. Most notably, neuroleptics produce catalepsy; however, buspirone failed to induce catalepsy and instead reversed this effect. Isolated case reports have described buspirone as causing movement disorders, but these patients were previously exposed to neuroleptic agents. Furthermore, buspirone has been used successfully to treat anxiety in parkinsonism without exacerbating existing movement problems. In psychotropic drug use, careful patient monitoring, complete drug histories, and a full appreciation for a drug's pharmacology are necessary to decipher any likelihood of a drug relation with an adverse effect.
多巴胺是一种影响运动功能的神经递质，多巴胺系统是运动障碍性疾病异常的焦点。许多具有多巴胺活性的精神药物的一个重要副作用是产生运动障碍；对于任何一种新的中枢神经系统药物，如氮杂螺环酮类抗焦虑药物，都需要仔细研究这个潜在问题。以原型药物丁螺环酮为代表的氮杂螺环酮类药物的药理学涉及几种不同的神经受体系统。目前的证据表明，丁螺环酮的抗焦虑活性是通过血清素能机制介导的。它对多巴胺受体也表现出一定的结合亲和力，这就需要在临床前试验、临床研究和病例报告中对丁螺环酮和抗精神病药物进行比较。尽管在一些生化研究中出现了相似之处，但长期使用后，抗精神病药物而非丁螺环酮会导致多巴胺受体增加。抗精神病药物通常在长期使用后产生这种变化，这被认为是导致迟发性运动障碍的关键因素。在标准的动物行为研究中，丁螺环酮的表现与抗精神病药物不匹配。最值得注意的是，抗精神病药物会产生僵住症；然而，丁螺环酮未能诱发僵住症，反而逆转了这种效应。个别病例报告描述丁螺环酮会导致运动障碍，但这些患者之前都接触过抗精神病药物。此外，丁螺环酮已成功用于治疗帕金森病患者的焦虑症，而不会加剧现有的运动问题。在使用精神药物时，仔细监测患者、了解完整的用药史以及充分了解药物的药理学知识对于判断药物与不良反应之间的任何关联可能性都是必要的。
