By the use of selective radioactively labeled agonist and antagonist substances, five subtypes of muscarinic receptors have been determined, named M–M (using an upper case M and subscript number). M, M, M receptors are coupled with G proteins, while M and M receptors are coupled with G proteins. There are other classification systems. For example, the drug pirenzepine is a muscarinic antagonist (decreases the effect of ACh), which is much more potent at M receptors than it is at other subtypes. The acceptance of the various subtypes proceeded in numerical order, therefore, earlier sources may recognize only M and M subtypes, while later studies  recognize M, M,[http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=2] and most recently M subtypes.