Dykstra L A, Picker M J, Powell K R
Department of Psychology, University of North Carolina, Chapel Hill 27599-3270.
Pharmacol Biochem Behav. 1990 Jul;36(3):639-44. doi: 10.1016/0091-3057(90)90269-n.
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.
在松鼠猴按照固定比率30的食物呈现时间表做出反应的过程中，对μ阿片受体激动剂吗啡、阿片受体拮抗剂纳洛酮以及混合作用阿片类药物环唑辛、N -烯丙基去甲左啡诺和喷他佐辛的异构体进行了研究。在猴子接受6毫克/千克/天吗啡的慢性给药方案之前、期间和之后，获取了所有药物的剂量 - 效应曲线。与慢性给药方案之前获得的剂量 - 效应曲线相比，慢性给药方案期间获得的吗啡剂量 - 效应曲线向右移动了0.5 - 1.0对数单位，而纳洛酮剂量 - 效应曲线向左移动了超过3对数单位。对于(+)-环唑辛、(+)-N -烯丙基去甲左啡诺以及(+)-或(-)-喷他佐辛，在慢性给药前和慢性给药后的剂量 - 效应曲线之间未观察到变化。N -烯丙基去甲左啡诺和环唑辛的(-)异构体向左移动了0.6 - 1.7对数单位。这些结果表明，环唑辛和N -烯丙基去甲左啡诺的(-)异构体具有μ拮抗剂特性，这些特性在慢性吗啡给药期间得以显现。
