title: Dose related effects of the kappa agonist U-50, 488H on behaviour, nociception and autonomic response in the horse.
abstract: Current opiate receptor theory suggests that kappa agonists should provide good analgesia without producing marked central nervous system stimulation. U-50,488H is an experimental narcotic analgesic that is a selective kappa agonist. In the present study, U-50,488H produced good analgesia in horses using both the skin twitch and hoof withdrawal reflex assays. Further, the analgesia was relatively long lasting (120 mins) compared to other mu-agonists tested in horses. The locomotor response to U-50,488H was less than observed with ethylketazocine and butorphanol, and has yielded the smallest locomotor response of any of the narcotic analgesics tested to date. Other work showed that the autonomic responses to U-50,488H were less than those of other narcotic analgesics, and that the analgesic response to this drug was blocked by naloxone. Based on its ability to produce analgesia with little other stimulatory action, U-50,488H shows promise of becoming a useful narcotic analgesic in equine medicine.
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Louisiana State University, Baton Rouge 70803.
authors.forename: S
authors.initials: S
authors.lastname: Kamerling
authors.forename: T
authors.initials: T
authors.lastname: Weckman
authors.forename: J
authors.initials: J
authors.lastname: Donahoe
authors.forename: T
authors.initials: T
authors.lastname: Tobin
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016314:Ethylketocyclazocine; D005260:Female; D005283:Fentanyl / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006736:Horses / Q000502:physiology*; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D009619:Nociceptors / Q000187:drug effects*; D011680:Pupil / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D012119:Respiration / Q000187:drug effects
chemical_list: D000700:Analgesics; D011759:Pyrrolidines; D016314:Ethylketocyclazocine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D003496:Cyclazocine; D005283:Fentanyl