Opioid agonists/antagonists in morphine-tolerant squirrel monkeys.
The mu-opioid agonist morphine, the opioid antagonist naloxone and the isomers of the mixed action opioids, cyclazocine, n-allylnormetazocine, and pentazocine were examined in squirrel monkeys responding under a fixed-ratio 30 schedule of food presentation. Dose-effect curves for all drugs were obtained prior to, during, and following a chronic regimen in which monkeys received 6 mg/kg/day of morphine. When compared to the dose-effect curves obtained prior to the chronic regimen, the morphine dose-effect curve obtained during the chronic regimen was shifted to the right 0.5-1.0 log unit, whereas the naloxone dose-effect curve shifted over 3 log units to the left. No changes were observed between the prechronic and chronic dose-effect curves for (+)-cyclazocine, (+)-n-allylnormetazocine, and (+)- or (-)-pentazocine. The (-) isomers of n-allylnormetazocine and cyclazocine shifted 0.6-1.7 log units to the left. These results suggest that the (-) isomers of cyclazocine and n-allylnormetazocine have mu antagonist properties which are revealed during chronic morphine administration.
Dykstra
L A
LA
Department of Psychology, University of North Carolina, Chapel Hill 27599-3270.
Picker
M J
MJ
Powell
K R
KR
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004361:Drug Tolerance; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D012453:Saimiri; D013237:Stereoisomerism
D000701:Analgesics, Opioid; D009270:Naloxone; D009020:Morphine