Jun 1, 1996

Antagonism of striatal muscarinic receptors inhibiting dopamine D1 receptor-stimulated adenylyl cyclase activity by cholinoceptor antagonist used to treat Parkinson's disease

British Journal of Pharmacology
M C Olianas, P Onali

Abstract

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 D1 receptor-stimulated adenylyl cyclase or the muscarinic receptor-mediated stimulation of [3H]-inositol phosphates ([3H]-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 [3H]-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 D1 receptor activation may be one of the mechanisms by which cholinoceptor blocking drugs exert their antiparkinsonian effect.

Mentioned in this Paper

Inositol Phosphates
Exertion
Tissue Membrane
Carboptic
Striatal Cell Bridges
Antagonist Muscle Action
Lentiform Nucleus Structure
Cholinergic Receptors
Antiparkinson Agents
Pharmacologic Substance

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