Association of the peptidase inhibitor RB 101 and a CCK-B antagonist strongly enhances antinociceptive responses.
The brain peptide cholecystokinin (CCK) has been shown to counteract the analgesic effects of morphine suggesting a physiological antagonism between opioid and CCK neural systems. This has been definitely demonstrated in this study by co-administration of the CCK-B selective antagonist L-365,260 with RB 101, a systemically active inhibitor of peptidases, which fully protects the endogenous opioids, the enkephalins, from their inactivation. The naloxone reversible analgesic effects induced by RB 101 in the mouse hot-plate and rat tail-flick tests were strongly increased by low doses of L-365,260. These results could have important clinical applications by reducing the efficient dose of RB 101, which has recently been shown to be practically devoid of morphine-like side-effects.
Maldonado
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Département de Pharmacochomie Moléculaire et Structurale, INSERM U266-CNRS URA D1500, Université René Descartes, Faculté des Sciences, Pharmaceutiques et Biologiques, Paris, France.
Derrien
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Noble
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F
Roques
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BP
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D020109:Devazepide; D004220:Disulfides / Q000494:pharmacology*; D004357:Drug Synergism; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010671:Phenylurea Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors
D000700:Analgesics; D001570:Benzodiazepinones; D004220:Disulfides; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; C074024:RB 101; C058121:L 365260; D010649:Phenylalanine; D002766:Cholecystokinin; D020109:Devazepide