可乐定局部应用的抗伤害作用

目的 探讨局部应用可乐定的抗伤害反应作用及其耐受性的产生。方法 观察了局部应用可乐定的抗伤害效应、药物处理时间与可乐定抗伤害效应间的关系、提前全身给予纳洛酮或育亨宾对可乐定抗伤害效应的影响及局部应用氯胺酮对可乐定抗伤害耐受发生的影响。结果 在药物局部处理过的小鼠尾部，可乐定产生了浓度相关性的抗伤害效应；局部应用可乐定的抗伤害效应的强度与局部暴露于药液的时间相关；育亨宾完全阻断了可乐定的抗伤害作用，纳洛酮则无明显影响；氯胺酮与可乐定同时局部给药对可乐定抗伤害耐受的产生没有影响。结论 局部应用可乐定可通过激活外周的 α2肾上腺素能受体产生浓度依赖性的抗伤害效应，避免了全身给药的副作用；反复给药能产生抗伤害耐受，局部应用氯胺酮未能阻止这种耐受的发生，说明外周NMDA受体没有参与耐受的发生。

Antinociceptive Effect of Local Use of Clonidine

Objective To investigate the antinociceptive effect and tolerance of clonidine when administered topically.Methods To observe antinociceptive actions of topical clonidine in mice,effect of exposure time on the antinociceptive actions of topical clonidine in mice,effect of systemic naloxone and yohimbine pretreatment on topical clonidine induced antinociception and the effect of topical ketamine on the development of antinociceptive tolerance to topical clonidine.Results Clonidine administration produced concentration-dependent antinociception.The antinociceptive effect of topical clonidine was dependent on the exposure time.Systemic pretreatment with yohimbine completely blocked the antinociceptive activity of topical clonidine.Systemic pretreatment with naloxone did not significantly alter the antinociceptive,activity of topical clonidine at any time across the 180 min testing period.Topical ketamine co-administered with topical clonidine did not prevent the development of tolerance to the antinociceptive effects of topical clonidine.Conclusion Topical administration of clonidine elicits concentration-dependent antinociception by blocking the emerging pain signals at peripheral terminals via alpha-2 adrenoceptors without producing the undesirable central side effects observed following the systemic administration.The ineffectiveness of topical ketamine to block topical clonidine antinociceptive tolerance suggests that peripheral NMDA receptors do not mediate local clonidine antinociceptive tolerance.