Modell J G, Tandon R, Beresford T P
Department of Psychiatry, University of Michigan, Ann Arbor.
J Clin Psychopharmacol. 1989 Oct;9(5):347-51.
The antimuscarinic antiparkinsonian agents are widely used in psychiatric practice to reduce the extrapyramidal motor symptoms caused by the neuroleptic antipsychotic medications. Although the antimuscarinic antiparkinsonian agents are effective in reducing extrapyramidal symptoms, their use in conjunction with neuroleptic treatment of psychosis has been reported to antagonize the therapeutic effects of the neuroleptic; there are also several reports of the antimuscarinic antiparkinsonian agents variously causing psychotic syndromes, mood elevating and stimulant effects, stereotypy, dyskinesia, behavioral agitation, and drug dependence in both psychiatric and normal populations. These drug-related phenomena are generally attributed to the antimuscarinic properties of these agents. A large body of data, however, has shown that the antimuscarinic antiparkinsonian agents also function as potent, indirect dopamine-agonists. Benztropine, the most widely prescribed of these medications, is one of the most potent known inhibitors of presynaptic dopamine reuptake. These antiparkinsonian agents also have potent agonist activity at the noradrenergic synapse, as well as minor activity at the serotonergic synapse. This paper reviews neuropharmacologic evidence suggesting that significant neurophysiologic effects can result from the dopaminergic--and possibly noradrenergic--activity of the antimuscarinic antiparkinsonian agents, similar in some cases to those observed with amphetamine. Greater attention to these properties may aid in interpretation of clinical and research observations involving these so-called "antimuscarinic" agents.
抗毒蕈碱类抗帕金森病药物在精神病学实践中广泛用于减轻抗精神病药物引起的锥体外系运动症状。尽管抗毒蕈碱类抗帕金森病药物在减轻锥体外系症状方面有效，但据报道，它们与精神病的抗精神病药物联合使用会拮抗抗精神病药物的治疗效果；也有几篇报道称，抗毒蕈碱类抗帕金森病药物在精神病患者和正常人群中会引起各种精神病综合征、情绪高涨和兴奋作用、刻板行为、运动障碍、行为激越及药物依赖。这些与药物相关的现象通常归因于这些药物的抗毒蕈碱特性。然而，大量数据表明，抗毒蕈碱类抗帕金森病药物还可作为强效的间接多巴胺激动剂发挥作用。这些药物中最常处方的苯海索是已知最强效的突触前多巴胺再摄取抑制剂之一。这些抗帕金森病药物在去甲肾上腺素能突触也具有强效激动剂活性，在5-羟色胺能突触也有较弱活性。本文综述了神经药理学证据，表明抗毒蕈碱类抗帕金森病药物的多巴胺能——可能还有去甲肾上腺素能——活性可产生显著的神经生理学效应，在某些情况下与苯丙胺观察到的效应相似。更多关注这些特性可能有助于解释涉及这些所谓“抗毒蕈碱”药物的临床和研究观察结果。
