Dopaminergic Activity of the Antimuscarinic Antiparkinsonian Agents

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.