The partial agonist properties of levocabastine in neurotensin-induced analgesia.
The antihistaminic drug levocabastine is a ligand for the low affinity neurotensin receptor (NTS2). Its intracerebroventricular administration to mice induced a significant analgesia in the writhing test but not in the hot plate test. In the writhing test, levocabastine decreased neurotensin-induced analgesia to a level not significantly different from the effects of levocabastine alone. In the hot plate test, levocabastine had no analgesic effect but completely reversed the neurotensin-induced analgesia. Mepyramine, another antihistaminic drug, did not share these levocabastine effects. Neither levocabastine nor mepyramine modified the colonic temperature or reversed the neurotensin-induced hypothermia. Thus, levocabastine behaves as a partial agonist at neurotensin NTS2 receptors, which are involved in visceral nociception, but not at yet unidentified neurotensin receptors involved in hypothermia.
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Unité de Neuropsychopharmacologie expérimentale UPRESA 6036 C.N.R. S., (IFRMP 23), Faculté de Médecine et Pharmacie, Site universitaire du Madrillet 76800, St. Etienne du Rouvray, France.
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Costentin
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D000698:Analgesia; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009496:Neurotensin / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D017288:Pain Threshold / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D011738:Pyrilamine / Q000494:pharmacology; D018028:Receptors, Neurotensin / Q000819:agonists*
D000700:Analgesics; D006634:Histamine H1 Antagonists; D010880:Piperidines; D018028:Receptors, Neurotensin; D009496:Neurotensin; C047340:levocabastine; D011738:Pyrilamine