Gringauz M, Rabinowitz R, Stav A, Korczyn A D
Department of Anesthesiology, Hillel Jaffe Medical Center, Hadera, 38100, Israel.
J Anesth. 2001;15(4):204-9. doi: 10.1007/s005400170004.
The increased use of opioids in the chronic treatment of pain, especially with oncologic patients, encourages the search for drugs with potent analgesic activity, but with minimal induced tolerance and cross-tolerance to morphine.
Four agonist-antagonist opioid derivatives (buprenorphine, butorphanol, nalbuphine, and cyclorphan) were examined. Tolerance to the analgesic effect of the four drugs and their cross-tolerance effects with morphine were evaluated in ICR albino mice by the "hot plate method". Measurements of the analgesic effect were taken before and after chronic treatment (of 14 days duration) with these drugs, as well as morphine.
All tested drugs produced tolerance after 14 days of treatment. Chronic treatment with morphine reduced the effects of nalbuphine and cyclorphan, but not those of buprenorphine and butorphanol. After 14 days treatment with buprenorphine and cyclorphan, the analgesic action of morphine was reduced, but this reduction did not occur after butorphanol and nalbuphine treatments.
Of the four agonist-antagonists tested, butorphanol seems to be least likely to produce cross-tolerance with morphine.
阿片类药物在慢性疼痛治疗中的使用增加，尤其是在肿瘤患者中，这促使人们寻找具有强效镇痛活性但诱导耐受性和对吗啡交叉耐受性最小的药物。
研究了四种激动剂 - 拮抗剂阿片类衍生物（丁丙诺啡、布托啡诺、纳布啡和环佐辛）。通过“热板法”在ICR白化小鼠中评估对这四种药物镇痛作用的耐受性及其与吗啡的交叉耐受性。在使用这些药物以及吗啡进行慢性治疗（持续14天）之前和之后测量镇痛效果。
所有测试药物在治疗14天后均产生耐受性。吗啡的慢性治疗降低了纳布啡和环佐辛的效果，但对丁丙诺啡和布托啡诺没有影响。在丁丙诺啡和环佐辛治疗14天后，吗啡的镇痛作用降低，但在布托啡诺和纳布啡治疗后未出现这种降低。
在所测试的四种激动剂 - 拮抗剂中，布托啡诺似乎最不可能与吗啡产生交叉耐受性。
