ANTAGONISM OF STRIATAL MUSCARINIC RECEPTORS INHIBITING DOPAMINE D-1 RECEPTOR-STIMULATED ADENYLYL-CYCLASE ACTIVITY BY CHOLINOCEPTOR ANTAGONISTS USED TO TREAT PARKINSONS-DISEASE
Mc. Olianas et P. Onali, ANTAGONISM OF STRIATAL MUSCARINIC RECEPTORS INHIBITING DOPAMINE D-1 RECEPTOR-STIMULATED ADENYLYL-CYCLASE ACTIVITY BY CHOLINOCEPTOR ANTAGONISTS USED TO TREAT PARKINSONS-DISEASE, British Journal of Pharmacology, 118(4), 1996, pp. 827-828
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.