Potency ratio for the inhibition of 3H-QNB and 3H-cis-methyldioxolane binding predicts agonist or antagonist activity on muscarinic receptors.
3H-Quinuclidinyl benzylate (3H-QNB) and 3H-cis-methyldioxolane (3H-CD) binding to cholinergic muscarinic receptors have been carried out on the same membrane preparation from the rat brain cortex. Inhibition of 3H-QNB and 3H-CD binding by cholinergic muscarinic agonists and antagonists has been studied with determination of the IC50 values for each ligand. Antagonists were as potent at inhibiting 3H-QNB binding as 3H-CD binding. Muscarinic agonists were much less potent at inhibiting 3H-QNB binding than 3H-CD binding. The ratio of the IC50 values for the inhibition of the binding of 3H-QNB and 3H-CD was between 1 and 10 for antagonists and between 500 and 5000 for agonists. It is suggested that the determination of this ratio predicts agonist or antagonist activity of unknown compounds and represents a useful tool for their screening.
Moret
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C
Department of Biochemical Pharmacology, Centre de Recherche Pierre Fabre, Castre, France.
Pastrie
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I
Briley
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D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D004148:Dioxolanes / Q000378:metabolism*; D004149:Dioxoles / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D010277:Parasympathomimetics / Q000494:pharmacology*; D011812:Quinuclidines / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*
D004148:Dioxolanes; D004149:Dioxoles; D010277:Parasympathomimetics; D011812:Quinuclidines; D011976:Receptors, Muscarinic; C024310:2-methyldioxolane; D011813:Quinuclidinyl Benzilate