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Antagonism of striatal muscarinic receptors inhibiting dopamine D 1 receptor‐stimulated adenylyl cyclase activity by cholinoceptor antagonists used to treat Parkinson's disease
Author(s) -
Olianas Maria C.,
Onali Pierluigi
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15474.x
Subject(s) - muscarinic acetylcholine receptor , muscarinic acetylcholine receptor m1 , adenylyl cyclase , pharmacology , muscarinic acetylcholine receptor m3 , chemistry , muscarinic acetylcholine receptor m5 , dopamine , receptor , muscarinic acetylcholine receptor m4 , dopamine receptor , muscarinic acetylcholine receptor m2 , endocrinology , biology , biochemistry
A number of cholinoceptor antagonists used in the treatment of Parkinson's disease were examined for their ability to antagonize either the muscarinic receptor‐mediated inhibition of dopamine D 1 receptor‐stimulated adenylyl cyclase or the muscarinic receptor‐mediated stimulation of [ 3 H]‐inositol phosphates ([ 3 H]‐IPs) formation in rat striatal membranes. The drugs were found to block the receptors inhibiting adenylyl cyclase activation with high affinity and more potently than those stimulating [ 3 H]‐IPs formation. Moreover, their rank order of potencies for the former effect showed good correlation with their clinical efficacies. These data suggest that the blockade of the muscarinic receptor‐mediated inhibition of striatal dopamine D 1 receptor activation may be one of the mechanisms by which cholinoceptor blocking drugs exert their antiparkinsonian effect.