title: The individual and combined effects of U50,488, and flurbiprofen axetil on visceral pain in conscious rats.
abstract: We examined the effects of U50,488, a kappa-opioid receptor agonist, and flurbiprofen axetil, a nonsteroidal antiinflammatory drug, in a visceral pain model using conscious rats. U50,488 produced visceral antinociception, but exaggerated the adverse effects on the central nervous system (CNS) at 0.9 mg/kg or more. Naloxone completely antagonized these effects. Flurbiprofen axetil produced visceral antinociception, but exaggerated the adverse effects on the CNS at 80 mg/kg. Coadministration of U50,488 (0.27 mg/kg) and flurbiprofen axetil (50 mg/kg) produced intense visceral antinociception without adverse effects on the CNS, implying therapeutic efficacies of coadministration of kappa-opioid receptor-agonists and nonsteroidal antiinflammatory drugs on visceral pain.
authors.affiliation: Department of Anesthesiology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan 113-8655. tyy-kitamura@m7.dion.ne.jp
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kitamura
authors.forename: Makoto
authors.initials: M
authors.lastname: Ogawa
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000627:therapeutic use*; D000009:Abdominal Muscles / Q000187:drug effects; D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002404:Catheterization; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005480:Flurbiprofen / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists; D012007:Rectum / Q000502:physiology
chemical_list: D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; D005480:Flurbiprofen; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C504422:flurbiprofen axetil