Tifluadom, a kappa-opiate agonist, acts as a peripheral cholecystokinin receptor antagonist.
Tifluadom, a benzodiazepine kappa-opiate agonist, stereoselectively inhibited the binding of 125I-CCK to pancreatic membranes (IC50 = 47 nM). Several other opiate agonists were ineffective. Scatchard analysis indicated the inhibition of CCK binding by tifluadom was competitive in nature. Tifluadom (1 microM) did not displace 125I-CCK binding to brain tissue or 125I-gastrin binding to fundic glands. In the isolated guinea pig gallbladder, tifluadom antagonized CCK-8 induced contractions with an estimated pA2 of 6.8. These data demonstrate that tifluadom is a peripherally selective CCK antagonist. This unique action could contribute to its reported analgesic and appetite stimulatory properties.
D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000187:drug effects; D005704:Gallbladder / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D010179:Pancreas / Q000187:drug effects; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000187:drug effects* / Q000378:metabolism; D011957:Receptors, Opioid / Q000187:drug effects*; D017473:Receptors, Opioid, kappa
D011949:Receptors, Cholecystokinin; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D001569:Benzodiazepines; C035470:tifluadom