High affinity of quinidine for a stereoselective microsomal binding site as determined by a radioreceptor assay |
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Authors: | S V Otton W Kalow P Seeman |
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Institution: | (1) Department of Pharmacology, Medical Sciences Building, University of Toronto, M5S 1A8 Toronto, Canada |
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Abstract: | Summary The techniques of the radioreceptor binding assay were applied to detect stereoselective binding of quinidine and quinine to a site on human liver microsomes. Binding of3H-dihydroquinidine was 50% inhibited by 20–100 nM quinidine, while its enantiomer quinine did not displace the3H-ligand at concentrations up to 500 nM. This stereoselectivity agreed with the affinity values measured by functional enzyme assays of cytochrome P450 activity using sparteine or debrisoquine as substrates.Acknowledgments. We thank C. Ulpian for advice and assistance. We also thank Dr M. Robinette of Metro Organ Retrieval and Exchange and Dr T. Inaba for making human hepatic tissue available. This work was supported by grants from the Medical Research Council of Canada. |
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Keywords: | Microsome human liver radioreceptor assay stereoselective binding 3H-dihydroquinidine quinidine quinine |
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