Yoburn B C, Inturrisi C E
Department of Pharmaceutical Sciences, College of Pharmacy & Allied Health Professions, St. John's University, Jamaica, NY 11439.
Life Sci. 1988;42(18):1689-96. doi: 10.1016/0024-3205(88)90034-3.
Chronic exposure to opioid antagonists increases the analgesic actions of opioids such as morphine. In the present studies, morphine's analgesic potency was increased (supersensitivity) following an 8 day subcutaneous naltrexone implant in mice, but not following a 1 day implant. Supersensitivity was maximal 24hr following the 8 day implant and declined linearly and had returned to control levels by 120hr. Implantation of naltrexone pellets for 8 days was found to increase the relative analgesic potency of methadone by 120%, while the lethal potency of cocaine was slightly (19%), but significantly, decreased. In contrast, identical treatment did not alter the potency of the benzodiazepine alprazolam to induce ataxia.
长期接触阿片类拮抗剂会增强吗啡等阿片类药物的镇痛作用。在本研究中，小鼠皮下植入纳曲酮8天后，吗啡的镇痛效力增强（超敏反应），但植入1天则无此现象。超敏反应在8天植入后24小时达到最大值，然后呈线性下降，至120小时时恢复到对照水平。发现植入纳曲酮丸8天可使美沙酮的相对镇痛效力提高120%，而可卡因的致死效力略有降低（19%），但具有显著性。相比之下，相同处理并未改变苯二氮䓬类药物阿普唑仑诱导共济失调的效力。
