Selective modulation of muscarinic receptor subtypes: therapeutic potential

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Abstract
Muscarinic receptors comprise five subtypes, each of which has a different distribution and function. The therapeutic utility of either activating or antagonising muscarinic receptors has long been recognised, although the clinical use of existing compounds is limited by their side-effects. Since these effects usually emanate from a lack of subtype discrimination, a concerted effort is underway to identify selective muscarinic receptor agonists and antagonists. Functionally-selective M1 agonists are now in clinical trials for cognitive disorders, some of which demonstrate an improvement in function. In terms of antagonists, several compounds are in advanced clinical evaluation for the treatment of smooth muscle disorders including urinary incontinence, irritable bowel syndrome and chronic obstructive pulmonary disease.