Functional and biochemical basis for multiple muscarinic acetylcholine receptors

1. The novel antimuscarinic compound pirenzepine (PZ) has generated considerable interest in the basis and the implications of muscarinic acetylcholine receptor (mAChR) heterogeneity. 2. [³H]PZ has been used extensively to identify and characterize the putative M₁ (high affinity for PZ) mAChR subtype, which predominates in central nervous system (CNS) and ganglia. 3. The heterogeneity sensed by PZ is not identical to the heterogeneity sensed by agonists. 4. Differences in effector coupling do not necessarily provide a simple explanation for the molecular basis of these putative M₁ and M₂ subtypes. 5. Therapeutic and untoward effects of muscarinic drugs may be mediated by independent mAChR subpopulations which may be pharmacologically exploited to produce more highly selective as well as efficacious new drugs.