Kappa antagonist properties of buprenorphine in the shock titration procedure.
Buprenorphine produced a dose-dependent antagonism of the selective kappa opioid agonist U50,488 in squirrel monkeys responding under the shock titration procedure. In one group of four monkeys, 0.003-0.01 mg/kg buprenorphine produced dose-dependent rightward shifts in the individual U50,488 dose-effect curves and increased the A50 value for U50,488 more than 2-fold in each monkey. Furthermore, 0.01 mg/kg buprenorphine antagonized a maximally effective dose of U50,488 in these monkeys. Buprenorphine (0.01-0.1 mg/kg) also produced rightward shifts in the group U50,488 dose-effect curve for a second group of three monkeys. Buprenorphine's antagonism of U50,488 was probably not a consequence of any mu opioid antagonist properties of buprenorphine in this procedure since (1) buprenorphine produced an inconsistent antagonism of the selective mu agonist fentanyl, and (2) the selective mu antagonist beta-funaltrexamine did not antagonize U50,488. These results support the hypothesis that buprenorphine has kappa antagonist activity in the shock titration procedure.
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Curriculum in Neurobiology, University of North Carolina, Chapel Hill 27599.
Dykstra
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D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D000818:Animals; D002047:Buprenorphine / Q000494:pharmacology*; D004597:Electroshock; D005283:Fentanyl / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D011759:Pyrrolidines / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D011957:Receptors, Opioid / Q000187:drug effects*; D017473:Receptors, Opioid, kappa; D012453:Saimiri
D000700:Analgesics; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D002047:Buprenorphine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C024524:beta-funaltrexamine; D005283:Fentanyl