Receptor binding profiles of some selective muscarinic antagonists.
The binding of hexahydrosiladifenidol, procyclidine, 4-DAMP (4-diphenylacetoxy-N-methylpiperidine) and AF-DX 116 to muscarinic receptors in the heart, ileum, urinary bladder, parotid gland and cerebral cortex from guinea pig was studied in competition experiments with (-)-[3H]QNB. The affinity of AF-DX 116 was higher in the heart than in the cortex and it was extremely low in the parotid gland. The affinities of hexahydrosiladefinidol, procyclidine and 4-DAMP were higher in the cortex and parotid gland than in the heart, bladder and ileum. Hexahydrosiladifenidol and 4-DAMP recognized two classes of muscarinic binding sites in the cortex. However, in contrast to functional data, binding results showed that 4-DAMP hexahydrosiladifenidol and procyclidine did not distinguish between the sites in the smooth muscles and those in the heart. Nevertheless, the present data support the view that the putative M2-receptors are heterogeneous, since the four drugs examined were found to distinguish between the muscarinic binding sites in the parotid gland and those in smooth muscles and heart.
Department of Pharmacology, R&D, KabiVitrum AB, Stockholm, Sweden.
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Nilvebrant
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Sparf
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D010306:Parotid Gland / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D011352:Procyclidine / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate; D011976:Receptors, Muscarinic / Q000187:drug effects*; D001743:Urinary Bladder / Q000187:drug effects
D010276:Parasympatholytics; D010880:Piperidines; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D011352:Procyclidine; C046773:hexahydrosiladifenidol; C048593:otenzepad