The theory, methods and relevance of muscarinic receptor binding studies

The development of receptor-specific ligands, radiolabelled to high specific activity has made possible the investigation of the binding of anti-muscarinic compounds to the muscarinic receptor in vitro. Binding of these compounds satisfies the criteria of saturability, and specificity for the muscarinic receptor, and their potencies for binding correlate with their potencies in inhibiting muscarinic responses in vivo. Whilst analysis of the binding data for 'classical' muscarinic antagonists indicate that they bind to a single, uniform population of binding sites within a given tissue, some anti-muscarinic compounds have been found to bind selectively to receptors in different tissues. Furthermore, pirenzepine binding in some preparations deviates from simple mass action behaviour indicating that it recognizes subclasses of receptors within tissues. The pharmacological profile of selective anti-muscarinic compounds compares well with their behaviour in binding studies and indicates that such studies can provide a simple and rapid primary screen for anti-muscarinic action of newly synthesised drugs.