双重功效镇痛药他喷他多的药理学研究与临床应用

Pharmacology and clinical application of analgesic tapentadol with a dual mode of action

他喷他多是一种新型双重作用方式的中枢性镇痛药.它既是"阿片受体激动药.又是去甲肾上腺素重吸收抑制药.对急性、炎性和慢性神经病理性疼痛的多种动物模型有镇痛作用,其效能介于吗啡和曲马朵之间,静脉注射或口服均能达到满意的血药浓度,且耐受良好。最常见的静脉注射相关不良反应有嗜睡、眩晕、口干和恶心。药理作用与曲马朵类似,但曲马朵是左旋、右旋对映异构体的外消旋混合物,起μ阿片受体激动和去甲肾上腺素重吸收抑制作用的是不同构型的对映异构体分子及其代谢产物;而他喷他多则不需要中间代谢过程,作为μ阿片受体激动药和去甲肾上腺素重吸收抑制药都是同样的分子在起作用。这就是为什么他喷他多疗效强于曲马朵的原因。

Tapentadol hydrochloride, a new centrally acting analgesic with a dual mode of action： mu-opioid receptor agonism and inhibition of norepinephrine reuptake. Tapentadol showed analgesic effects in a wide range of animal models of acute, inflammatory and chronic neuropathic pain. Its potency was between that of morphine and tramadol. The drug achieved satisfactory serum levels after both IV and oral administration. It was generally well tolerated. The most common adverse effects associated with increasing IV tapentadol were sleepiness, vertigo, dry mouth, and nausea. Tapentadol＇s mu agonism and inhibition of norepinephrine reuptake make it similar to tramadol. However. tramadol consists of a racemic mixture of negative and positive enantiomers. The drug＇s mu agonism depends on transformation of the positive enantiomer into an active metabolite. The norepinephrine reuptake inhibition is mediated by the negative enantiomer. Tapentadol, on the other hand, requires no metabolism to be pharmacologically active. Both its mu-receptor agonism and norepinephrine reuptake inhibition are mediated by the same molecule. That is why its potency is higher than tramadol.