Facilitatory effect of naloxone and involvement of specific ligand-opiate receptor system in the antinociceptive effects of non-opioid drugs.
The facilitatory effects exerted by naloxone on a nociceptive reaction (jumping) in the hot plate test was not modified by three phosphodiesterase inhibitors, theophylline, Ro-20-1724 and I.C.I. 63197 which had on themselves different effects on the latency of jumping. The facilitatory effects of naloxone were not diminished by neuroleptics, cholinergic agonists or miscellaneous drugs (baclofen, indomethacin, ketoprofen, n-dipropylacetate, diazepam and potassium chlorazepate). Naloxone antagonized the antinocieceptive effects of neuroleptics in different patterns. No competitive component could be observed with haloperidol, whereas such a phenomenon was apparent with benperidol. Pimozide was an intermediary case. The antinociceptive effects of two cholinergic agonists, arecoline and eserine were antagonized by naloxone and stereospecifically by the (-) isomer, Mr 2266. The (+) isomer, Mr 2267 was inactive. The antagonism by the opioid antagonists of the antinociceptive effects of cholinergic agonists appeared to be of a competitive type. Thus the facilitatory effects of naloxone did not apparently involve activation of adenyl cyclase or the mediation of dopaminergic or cholinergic (neural) structures. The antinociceptive effects of benperidol and pimozide but not of haloperidol might result from the triggering of specific opiate receptors and those of cholinergic agonists from such a triggering and/or from release of endogenous ligands.
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001544:Benperidol / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects*; D013566:Sympathomimetics / Q000494:pharmacology
D000700:Analgesics; D010726:Phosphodiesterase Inhibitors; D011957:Receptors, Opioid; D013566:Sympathomimetics; D010868:Pimozide; D009270:Naloxone; D007980:Levodopa; D001544:Benperidol; D001418:Baclofen; D006220:Haloperidol