title: Flupirtine antinociception in the dog is primarily mediated by nonopioid supraspinal mechanisms.
abstract: Flupirtine is a novel analgesic recently introduced with therapy. The present study assessed the role of opioid mechanisms in flupirtine-induced antinociception, localized its site of action along the neuraxis and evaluated its relative potency. Analgesic and general behavioral effects of flupirtine (0.3-10 mg/kg i.v.) were compared to those of the opioid analgesic pentazocine (0.3-5 mg/kg i.v.) in chronic spinal dogs. Flupirtine was slightly less effective than pentazocine in depressing the supraspinally mediated skin twitch nociceptive reflex. But in contrast to pentazocine, flupirtine only weakly depressed the flexor reflex, a spinally mediated nociceptive reflex. Statistically reliable potency estimates for antinociception were not obtained. Both drugs constricted pupils and lowered body temperature. In drug interaction studies, a relatively high dose (1 mg/kg i.v.) of the opioid antagonist naltrexone antagonized the effects of pentazocine but not those of flupirtine. It is concluded that flupirtine-induced antinociception is not opiate-receptor mediated, that its antinociceptive actions occur primarily at supraspinal sites and that its potency is less than that of pentazocine in the dog.
authors.affiliation: Neuropharmacology Laboratory, National Institute on Drug Abuse, Addiction Research Center, Baltimore, MD 21224.
authors.forename: D B
authors.initials: DB
authors.lastname: Vaupel
authors.forename: B
authors.initials: B
authors.lastname: Nickel
authors.forename: K
authors.initials: K
authors.lastname: Becketts
mesh_terms: D000631:Aminopyridines / Q000009:adverse effects / Q000494:pharmacology*; D000700:Analgesics / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D003655:Decerebrate State; D004285:Dogs; D005260:Female; D009271:Naltrexone / Q000494:pharmacology; D010423:Pentazocine / Q000494:pharmacology; D012018:Reflex / Q000187:drug effects; D013696:Temperature; D013997:Time Factors
chemical_list: D000631:Aminopyridines; D000700:Analgesics; D009271:Naltrexone; C034161:flupirtine; D010423:Pentazocine