Antiparkinsonian benefit is generally attributed to inhibition of central muscarinic acetylcholine receptors. For instance, Duvoisin and Katz reported an antiparkinsonian benefit to benztropine and scopolamine, both centrally acting anticholinergics, with an exacerbation of parkinsonism after a trial of physostigmine, a centrally acting anticholinesterase inhibitor. In contrast, peripheral anticholinergics (methyl scopolamine and propantheline) and a peripheral anticholinesterase (edrophonium) did not affect parkinsonian symptoms (74). Details of how centrally acting anticholinergics can modify PD symptoms, usually attributed to dopaminergic deficiency, remain unclear.
Abnormalities in the central acetylcholine neurotransmitter system have been described in PD patients (87,88). An oversimplified, but clinically useful, conceptualization is that the anticholinergic use corrects an imbalance between dopamine and acetylcholine (89). The depleted nigrostriatal dopaminergic system in PD causes a relative increase in striatal acetylcholine-dopamine ratio, which can be normalized by the use of anticholinergics. The clinical consequences of disrupted neurotransmitter ratios are not precisely known. Other proposed mechanisms include inhibition of dopamine reuptake (90) and mild NMDA glutamate antagonism (91). The clinical significance of these findings remains to be determined.
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