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Cooperativity pattern in the interaction of the antiestrogen drug clomiphene with the Muscarinic receptors

G Ben-Baruch, G Schreiber and M Sokolovsky

The possible interaction between the muscarinic receptors and the antiestrogenic drug clomiphene citrate was investigated in competition experiments using the highly specific tritiated antagonist N-methyl-4- piperidyl benzilate (4-NMPB) in various regions of rat brain. It was found that clomiphene can displace muscarinic antagonists from their receptor-ligand complexes. Binding analyses as well as determinations of the kinetics of dissociation of [3H]4-NMPB-receptor complexes indicate the binding of more than one molecule of clomiphene in a positively cooperative pattern. These findings suggest that the nonsteroidal antiestrogenic drugs, e.g., clomiphene, might exert their effects not only through the specific estrogen receptor but also in conjunction with the muscarinic system.

Volume 21, Issue 2, pp. 287-293, 03/01/1982
Copyright © 1982 by American Society for Pharmacology and Experimental Therapeutics




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