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.