Butorphanol, levallorphan, nalbuphine and nalorphine as antagonists in the squirrel monkey.
The effects of several mixed-action opioid agonist/antagonists were examined alone and in combination with the mu-opioid agonist l-methadone and the kappa-opioid agonist, trans-3,4-dichloro-N-methyl-N[2-(1-pyrrolidinyl)cyclohexyl]benzeneace tam ide (U50,488). Effects were examined in squirrel monkeys responding under a schedule of shock titration. Under this procedure shock was scheduled to increase once every 15 sec from 0.01 to 3.7 mA in 30 steps. Five responses on a lever during the 15-sec shock period terminated the shock for 15 sec, after which the shock resumed at the next lower intensity. The intensity below which the monkeys maintained the shock 50% of the time (median shock level) was determined. l-Methadone and U50,488 produced dose-dependent increases in median shock level. Nalbuphine, butorphanol and levallorphan also increased median shock level, but these increases were much smaller than those observed with l-methadone or U50,488. Nalorphine and naltrexone did not increase median shock level. Butorphanol, levallorphan, nalbupine, nalorphine and naltrexone all produced parallel, rightward shifts in both the l-methadone and U50,488 dose-effect curves. The apparent pA2 values obtained for naltrexone in combination with l-methadone (7.7) were at least one log unit larger than those obtained for naltrexone in combination with U50,488 (6.5). Similar differences were revealed for nalbuphine in combination with l-methadone (6.1) and U50,488 (5.2) as well as for nalorphine in combination with l-methadone (6.0) and U50,488 (5.5).(ABSTRACT TRUNCATED AT 250 WORDS)
Dykstra
L A
LA
Department of Psychology, University of North Carolina, Chapel Hill.
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D002077:Butorphanol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007977:Levallorphan / Q000494:pharmacology*; D008297:Male; D008691:Methadone / Q000037:antagonists & inhibitors; D009019:Morphinans / Q000494:pharmacology*; D009266:Nalbuphine / Q000494:pharmacology*; D009269:Nalorphine / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D011759:Pyrrolidines / Q000037:antagonists & inhibitors; D011957:Receptors, Opioid / Q000187:drug effects*; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D012453:Saimiri
D009019:Morphinans; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D007977:Levallorphan; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009266:Nalbuphine; D002077:Butorphanol; D009269:Nalorphine; D008691:Methadone