Effect of peptides on the development of tolerance to buprenorphine, a mixed opiate agonist-antagonist analgesic.
The subcutaneous administration of buprenorphine to male Sprague-Dawley rats produced a dose-dependent analgesia and hyperthermia in a dose range of 0.25-2 mg/kg. The subcutaneous administration of buprenorphine (0.5 mg/kg) twice a day for 4 days resulted in the development of tolerance to its analgesic and hyperthermic actions. Daily administration of melanotropin release inhibiting factor (Pro-Leu-Gly-NH2) or cyclo (Leu-Gly) (2 mg/kg s.c.) for 4 days, inhibited the development of tolerance to buprenorphine, as evidenced by greater analgesic and hyperthermic responses to buprenorphine in peptide-treated than in vehicle-treated buprenorphine-tolerant rats. The repeated injections of peptides did not alter the analgesic or the hyperthermic response to buprenorphine in non-tolerant rats. These studies suggest the possible role of hypothalamic peptides in blocking the development of tolerance to the pharmacological effects of buprenorphine, a potent analgesic agent.
D000700:Analgesics; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002047:Buprenorphine / Q000494:pharmacology*; D004347:Drug Interactions; D004361:Drug Tolerance; D008297:Male; D009019:Morphinans / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000700:Analgesics; D009019:Morphinans; D010455:Peptides; D002047:Buprenorphine