Delta opioid antagonist effects of buprenorphine in rhesus monkeys.
Buprenorphine is an opioid with high affinity for delta, mu and kappa opioid receptors. The delta receptor-mediated effects of buprenorphine have not been studied. Thus, the present study examined the delta receptor-mediated effects of buprenorphine in rhesus monkeys. assays of receptor binding and agonist-stimulated GTP S binding confirmed that buprenorphine had high affinity for, and low efficacy at, delta receptors. In an assay of schedule-controlled responding for food presentation in four monkeys, buprenorphine produced little effect alone, but it antagonized the effects of the delta agonist SNC80, the mu agonist morphine and the kappa agonist U50,488. Buprenorphine was approximately 30-fold less potent as a delta antagonist than as a mu or kappa antagonist. In three monkeys trained to discriminate SNC80 from saline, buprenorphine alone produced only saline-appropriate responding, and buprenorphine pretreatment antagonized the discriminative stimulus effects of SNC80. In a fourth monkey, buprenorphine produced a partial substitution for SNC80 that could be blocked by the delta-selective antagonist naltrindole but not by the mu-selective antagonist quadazocine. These results indicate that, in rhesus monkeys, buprenorphine has very low efficacy at delta receptors, and that buprenorphine produces delta receptor-mediated effects with lower potency than it produces mu or kappa receptor-mediated effects.
Negus
S S
SS
Alcohol and Drug Abuse Research Center, Harvard Medical School - McLean Hospital, Belmont, Massachusetts 02478-9106, USA.
Bidlack
J M
JM
Mello
N K
NK
Furness
M S
MS
Rice
K C
KC
Brandt
M R
MR
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002047:Buprenorphine / Q000494:pharmacology*; D002460:Cell Line; D003216:Conditioning, Operant / Q000187:drug effects*; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005502:Food; D066298:In Vitro Techniques; D008253:Macaca mulatta; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors*; D017473:Receptors, Opioid, kappa / Q000187:drug effects; D017450:Receptors, Opioid, mu / Q000187:drug effects; D012055:Reinforcement Schedule
D000701:Analgesics, Opioid; D001549:Benzamides; D010879:Piperazines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D002047:Buprenorphine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer