美普他酚及其同分异构体对角叉菜胶引起的炎症大鼠具有抗热痛敏作用

实验以清醒大鼠的缩腿潜伏期为指标,观察了腹腔注射美普他酚及其同分异构体112824和112825对角叉菜胶引起的热痛敏的影响.外周炎症由单侧足底注射角叉菜胶(2 mg/100 μl)引起.注射角叉菜胶3 h后,注射侧后肢局部红肿及热痛过敏反应达到高峰,持续数小时.腹腔注射0.1 mg/kg美普他酚对炎症和非炎症侧后肢的缩腿潜伏期无明显影响(P＞0.05,n=8).腹腔注射1mg/kg和10 mg/kg美普他酚对炎症和非炎症侧后肢产生明显的抗痛敏和抗伤害效应,且对炎症侧缩腿反应的抑制(抗痛敏)作用明显强于非炎症侧(抗伤害)(P＜0.05,n=8～11).预先腹腔注射1.5 mg/kg纳洛酮明显阻断美普他酚引起的抗伤害和抗痛敏效应.腹腔注射美普他酚的同分异构体112824(1 mg/kg)和112825(1.5 ms/kg)可产生与美普他酚类似的抗痛敏作用,该效应可被预先腹腔注射1.5 mg/kg纳洛酮完全阻断.提示美普他酚及其同分异构体具有明显抗伤害和抗痛敏作用,且以后者为强.该作用主要通过mu阿片受体介导.本研究为扩展美普他酚及其同分异构体在临床上的应用提供了依据.

Antinociceptive effects of meptazinol and its isomers on carrageenan-induced thermal hyperalgesia in rats

Using the latency of paw withdrawal (PWL) from a noxious thermal stimulus as a measure of hyperalgesia, the effects of i.p. injection of meptazinol and its isomers, 112824 and 112825, on carrageenan-induced thermal hyperalgesia were studied in awaked carrageenan-inflamed rats. Peripheral inflammation was induced by intraplantar (i.pl.) injection of carrageenan (2 mg/100 microl) into one hindpaw in rats. Carrageenan produced marked inflammation (edema and erythema) and thermal hyperalgesia in the injected paws, which peaked at 3 h after injection and showed little change in magnitude for another 3 h. Injection of 0.1 mg/kg meptazinol (i.p.) at 3 h after carrageenan had no effect on the PWLs of either inflamed or non-inflamed hindpaw during the next 100 min (P>0.05, n=8). At the dosage of 1 and 10 mg/kg, meptazinol produced marked anti-nociception and anti-hyperalgesia in non-inflamed and inflamed hindpaw, respectively (P<0.05, n=8-11). The prolonging effect of meptazinol on PWL in inflamed hindpaw was more potent than that in non-inflamed hindpaw. Pre-administration of 1.5 mg/kg naloxone significantly antagonized meptazinol-induced anti-nociception and anti-hyperalgesia. Intraperitoneal injection of an isomer of meptazinol, 112825 (1.5 mg/kg), but not 112824 (1 mg/kg), markedly increased the PWL of the non-inflamed hindpaw. Nevertheless, both the isomers produced similar anti-hyperalgesic effect to that of meptazinol (P<0.05, n=8), which was completely reversed by naloxone (1.5 mg/mg). The results suggest that meptazinol and its isomers have anti-nociceptive and anti-hyperalgesic properties with the former more potent. The effects are mainly mediated by mu opioid receptors. This study provides an important clue for extending clinical utilization of meptazinol and its isomers.