Molecular Pharmacology, Vol 13, 533-540, Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics

Interaction of Loperamide with [³H]Naloxone Binding Sites in Guinea Pig Brain and Myenteric Plexus

¹ Department of Biological Research, Searle Laboratories, Chicago, Illinois 60680

The effects of morphine, naloxone, and loperamide on the binding of [³H]naloxone to the opiate receptor site(s) in guinea pig brain and myenteric plexus homogenates in the presence of sodium were studied. Results obtained from morphine and naloxone binding studies were consistent with the hypothesis of a single population of receptor sites. Scatchard plots prepared from the data for loperamide binding, however, indicated two possible populations of binding sites, only one of which was readily accessible to loperamide. Loperamide- and morphine-induced inhibition of the electrically stimulated contracting guinea pig ileal longitudinal muscle indicated only one site of action. The results of these experiments suggest that loperamide is bound stereospecifically to two populations of binding sites, both of which may be involved in producing opiate-like pharmacological effects in the longitudinal muscle preparation.

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ACKNOWLEDGMENTS The authors wish to thank Taft West, Ron Kochman, Arni Miller, Rosemary Auer, and Hitu Desai for their technical assistance.