Reversal by beta-funaltrexamine and 16-methyl cyprenorphine of the antinociceptive effects of opioid agonists in the mouse and guinea-pig.
The present study compared the effects of two opioid antagonists, beta-funaltrexamine (beta-FNA) and 16-methyl cyprenorphine (RX8008M) on the antinociception produced by a range of opioid agonists in the abdominal constriction test in the mouse and the paw pressure test in the guinea-pig. Both antagonists produced large shifts in the dose-response curves to the mu-agonists, morphine and fentanyl, confirming their mu-antagonist activity. Neither antagonist produced any antagonism of the antinociceptive effects of the selective kappa-agonists U50488, U69593 and tifluadom, in the mouse. However, RX8008M produced small shifts in the dose-response curves to these agonists in the guinea-pig, which seems more likely to reflect mu-receptor activity of the agonists in the guinea-pig than lack of selectivity of the antagonists. Both beta-FNA and RX8008M produced some antagonism of bremazocine, ethyl-ketocyclazocine, proxorphan and butorphanol, indicating that these agonists have a prominent mu-receptor component to their antinociceptive actions.
Hayes
A G
AG
Department of Neuropharmacology, Glaxo Group Research Ltd, Ware, Hertfordshire, U.K.
Birch
P J
PJ
D000005:Abdomen; D000818:Animals; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D009019:Morphinans / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology
D009019:Morphinans; D009292:Narcotic Antagonists; D009294:Narcotics; C051207:16-methylcyprenorphine; D009271:Naltrexone; C024524:beta-funaltrexamine