胍丁胺代谢产物腐胺对吗啡镇痛、耐受和依赖的影响

目的 观察腐胺对吗啡镇痛、耐受及依赖的影响，探讨腐胺治疗阿片耐受性和依赖性的潜力。方法 小鼠醋酸扭体模型和55℃热板法测痛阈；吗啡恒定剂量给药制备耐受模型，55℃热板法测痛阈；吗啡递增剂量给药制备依赖模型，纳洛酮催促观察戒断症状，以胍丁胺（40 mg·kg^-1，ig）为阳性对照药，腐胺灌胃给药剂量分别为10，20，40，80 mg·kg^-1。结果 在小鼠醋酸扭体模型中腐胺具有镇痛作用；而在小鼠55℃热板实验中，腐胺本身无镇痛作用，能较弱地增强吗啡镇痛；腐胺能够减弱吗啡耐受的形成，对已形成的吗啡耐受也有治疗作用；腐胺能够减弱吗啡躯体依赖的形成和表达。结论 腐胺和胍丁胺具有相似的生物学活性，具有治疗阿片耐受和依赖的潜力。

Effects of agmatine metabolite putrescine on morphine analgesia,tolerance and dependence

Objective To study the effects of putrescine on morphine pharmacological actions, such as analgesia, tolerance and dependence, and make sure if putrescine has potential of treating morphine tolerance and dependence. Methods Morphine analgesia was determined in acetic acid writhing and 55℃ hot plate test. Constant dose of morphine was administrated for tolerance model and 55℃ hot plate test was used for determining morphine analgesia. An ascending dose of morphine administration was used in physical dependence model and naloxone was injected to observe withdrawal symptom. Agmatine was used as positive control. The intragastric administration regimen of putrescine was 10,20,40 and 80 mg·kg^-1. Results In mouse acetic acid writhing model, putrescine produced analgesia. In hot plate test, putrescine didn′t produce analgesia, but could potentiate morphine analgesia weakly. Putrescine could attenuate the development of morphine tolerance, and treat morphine tolerance which was developed. In addition, putrescine could attenuate the development and expression of morphine physical dependence. Conclusion Putrescine has similar biological activities to agmatine. It suggests that putrescine has potential of treating morphine tolerance and dependence.