The relative selectivity of anticholinergic drugs for the M1 and M2 muscarinic receptor subtypes


  • Dr. Robert E. Burke

    Corresponding author
    1. Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, U.S.A.
    • Department of Neurology, College of Physicians and Surgeons, Columbia University, 710 W 168th St, New York, NY 10032, U.S.A.
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Anticholinergic drugs are used to treat a number of neurologic disorders, including parkinsonism, vestibular disturbances, and dystonia. Traditionally, these drugs have been thought to act in similar fashion, as competitive antagonists at a single class of muscarinic receptors, and not to differ significantly in their therapeutic efficacy. Recently, however, pharmacologic studies have shown that the novel antagonist pirenzepine is capable of recognizing heterogeneity among muscarinic receptors; high-affinity pirenzepine sites have been classified as M1 sites and low-affinity sites as M2. This study examined whether the anticholinergics currently available for treatment of neurologic symptoms have selectivity for these subtypes and whether they differ in their degree of selectivity; the study showed that these drugs do demonstrate selectivity. All had greater affinity for the M1 site, indicated by higher affinity for rat forebrain membranes, where M1 predominates, than hindbrain preparations, where M2 predominates. The degree of selectivity varied greatly; some compounds, such as ethopropazine, had little M1 selectivity, whereas others, such as scopolamine, trihexyphenidyl, and biperiden, were quite selective, like pirenzepine. It is unknown whether these differences in selectivity have any immediate therapeutic implications. However, these results support the emerging concept of muscarinic receptor subtypes and the prospect of developing more selective agents, with enhanced therapeutic efficacy.