ANTAGONISM OF STRIATAL MUSCARINIC RECEPTORS INHIBITING DOPAMINE D-1 RECEPTOR-STIMULATED ADENYLYL-CYCLASE ACTIVITY BY CHOLINOCEPTOR ANTAGONISTS USED TO TREAT PARKINSONS-DISEASE

A number of cholinoceptor antagonists used in the treatment of Parkins on's disease were examined for their ability to antagonize either the muscarinic receptor-mediated inhibition of dopamine D-1 receptor-stimu lated adenylyl cyclase or the muscarinic receptor-mediated stimulation of [H-3]-inositol phosphates [(H-3]-IPs) formation in rat striatal me mbranes. The drugs were found to block the receptors inhibiting adenyl yl cyclase activation with high affinity and more potently than those stimulating [H-3]-IPs formation. Moreover, their rank order of potenci es for the former effect showed good correlation with their clinical e fficacies. These data suggest that the blockade of the muscarinic rece ptor-mediated inhibition of striatal dopamine D-1 receptor activation may be one of the mechanisms by which cholinoceptor blocking drugs exe rt their antiparkinsonian effect.