苯甲酸利扎曲普坦鼻用温度-离子敏感型原位凝胶对偏头痛大鼠行为、痛域及血管活性物质的影响

Effect of Thermo-ion Sensitive In-situ Gel of Rizatriptan Benzoate for Intranasal Administration on the Behavior,Pain Threshold and Active Substances in Plasma in Migrainous Rats

目的:探讨苯甲酸利扎曲普坦(RB)鼻用温度-离子敏感型原位凝胶对偏头痛大鼠的行为、痛域及血管活性物质的影响。方法:采用电刺激法在清醒大鼠体内建立偏头痛模型。将模型大鼠按数字法随机分为3组:RB鼻用温度-离子敏感型原位凝胶(2.5 mg·kg^-1)组、RB溶液(2.5 mg·kg^-1)组、模型(生理盐水)组,每组10只,于电刺激前用50μl平头微量注射器经鼻给予相应药物。另取10只未造模大鼠设为空白组。各组分别施加频率为6 Hz、电压为3 V、脉宽为0.25 ms的电刺激,持续时间为1 h,连续5 d。对电刺激后大鼠行为、痛域及降钙素基因相关肽(CGRP)、内皮素(ET)、一氧化氮(NO)含量进行观测。结果:与模型相比,RB两种鼻用制剂均可明显改善电刺激后大鼠行为,增加机械及温度刺激痛域,并显著降低血浆中CGRP、ET、NO含量(P<0.05或P<0.01);与RB溶液相比,RB原位凝胶呈现更好的改善作用(P<0.05)。结论:RB鼻用温度-离子敏感型原位凝胶在偏头痛大鼠模型中有较好的治疗作用。

Objective: To explore the effects of thermo-ion sensitive in-situ gel of rizatriptan benzoate(RB) for intranasal administration on the behavior,pain threshold and active substances in plasma in migrainous rats.Methods: Migraious rat model was established by electric stimulation in clear rats.The model rats were randomly divided into 3 groups: RB nasal thermo-ion sensitive in situ gel(2.5 mg·kg^-1) group,RB solution(2.5 mg·kg^-1) group and the model(normal saline) group with 10 rats in each group.Before the electrical stimulation,the corresponding drug was given through the nose with a 50 μl flat-headed micro-injector.Another 10 rats without model were set as the blank group.Each group was stimulated with a frequency of 6 Hz,a voltage of 3 V and a pulse width of 0.25 ms lasting for 1 h for 5 days.The changes of behavior,pain threshold and the contents of calcitonin gene-related peptide(CGRP),endothelin(ET) and nitric oxide(NO) in plasma in migrainous rats were observed after the electrical stimulation.Results: Compared with the model group,the two RB nasal preparations both could improve the behavior,increase the pain threshold and decrease the contents of CGRP,ET and NO in plasma in rats after the electric stimulation(P<0.05 or P<0.01),and the effects of RB thermo-ion sensitive in-situ gel were better than those of RB solution(P<0.05).Conclusion: RB thermo-ion sensitive in-situ gel for nasal administration shows promising efficacy in migrainous rats.