title: Antagonist effects of beta-funaltrexamine and naloxonazine on alfentanil-induced antinociception and muscle rigidity in the rat.
abstract: Alfentanil is a potent and short-acting mu opioid agonist that produces both antinociceptive effects and muscle rigidity. In the present study, the susceptibility of alfentanil-induced antinociception and rigidity to antagonism by the selective mu antagonist beta-funaltrexamine and the selective mu-1 antagonist naloxonazine was examined. Alfentanil (37.7-150.0 micrograms/kg) produced a dose-dependent increase both in antinociception as measured by the warm-water tail-dip assay and in rigidity as measured by electromyographic recording of the gastrocnemius muscle. Both beta-funaltrexamine (10.0 and 20.0 mg/kg) and naloxonazine (7.5 and 15.0 mg/kg) produced dose-dependent and parallel rightward shifts in the alfentanil dose-effect curves for both antinociception and rigidity. Furthermore, the alfentanil dose-effect curves for antinociception and rigidity were shifted to the right to a similar degree by any given pretreatment. These results suggest that alfentanil-induced antinociception in the warm-water tail-dip test and rigidity are mediated by pharmacologically similar populations of opioid receptors. More specifically, these results suggest that mu-1 opioid receptors mediate both alfentanil-induced antinociception and rigidity.
authors.affiliation: Department of Neuropharmacology, Scripps Research Institute, La Jolla, California.
authors.forename: S S
authors.initials: SS
authors.lastname: Negus
authors.forename: G W
authors.initials: GW
authors.lastname: Pasternak
authors.forename: G F
authors.initials: GF
authors.lastname: Koob
authors.forename: M B
authors.initials: MB
authors.lastname: Weinger
mesh_terms: D015760:Alfentanil / Q000037:antagonists & inhibitors*; D000698:Analgesia; D000818:Animals; D004576:Electromyography; D008297:Male; D009127:Muscle Rigidity / Q000139:chemically induced* / Q000503:physiopathology; D009270:Naloxone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009292:Narcotic Antagonists; D015760:Alfentanil; D009270:Naloxone; D009271:Naltrexone; C024524:beta-funaltrexamine; C034643:naloxonazine