Chen J Q, Jin W Q, Chi Z Q
Shanghai Institute of Materia Medica, Chinese Academy of Science.
Zhongguo Yao Li Xue Bao. 1990 Nov;11(6):488-91.
A rapid and simple method for the quantitative determination of opioid dependence and tolerance in the guinea pig ileum was introduced. Dependence, as indicated by a strong contraction of the ileum when challenged with naloxone, was produced by incubating ileum from native guinea pig with opioid at 37 degrees C for 1-6 h. The response of the ileum to naloxone was time-dependent and directly related to the normorphine concentration in the incubation fluid (10-1000 nmol/L) and to the challenge dose of naloxone (10-1000 nmol/L). There were lower naloxone-precipitated withdrawal responses in the guinea pig ileum incubated with pethidine, nalorphine and ohmefentanyl than with fentanyl, U50488H and morphine. Buprenorphine showed no withdrawal response. In spite of rapid development of dependence, segments of ileum incubated with normorphine at low concentration (10-300 nmol/L) showed no or slight tolerance to normorphine (3-fold). Only by incubating with high concentration of normorphine (1 mumol/L) was high tolerance detected. The results indicate that opioid dependence and tolerance do not develop in parallel.
介绍了一种快速简便的定量测定豚鼠回肠中阿片类药物依赖性和耐受性的方法。通过将豚鼠回肠与阿片类药物在37℃孵育1 - 6小时产生依赖性，用纳洛酮激发时回肠强烈收缩即表明存在依赖性。回肠对纳洛酮的反应呈时间依赖性，且与孵育液中去甲吗啡浓度（10 - 1000 nmol/L）以及纳洛酮激发剂量（10 - 1000 nmol/L）直接相关。与芬太尼、U50488H和吗啡相比，用哌替啶、烯丙吗啡和奥芬太尼孵育的豚鼠回肠中，纳洛酮诱发的戒断反应较低。丁丙诺啡未显示出戒断反应。尽管依赖性发展迅速，但用低浓度（10 - 300 nmol/L）去甲吗啡孵育的回肠段对去甲吗啡未显示出或仅有轻微耐受性（3倍）。只有用高浓度（1 μmol/L）去甲吗啡孵育时才检测到高耐受性。结果表明，阿片类药物依赖性和耐受性并非平行发展。
