Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Epilepsy Behav. 2010 Nov;19(3):290-5. doi: 10.1016/j.yebeh.2010.08.006. Epub 2010 Sep 28.
In the present study, the effects of tramadol on pentylenetetrazole (PTZ)-induced seizures and involvement of nitric oxide (NO) were assessed in mice. To determine the threshold for clonic seizures, PTZ was administered intravenously. Tramadol was administered intraperitoneally (0.5-50mg/kg) 30 minutes prior to induction of seizures. The effects of the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 0.5, 1, 5, and 10mg/kg), the nitric oxide precursor L-arginine (10, 30, and 60 mg/kg), and the nonspecific opioid receptor antagonist naloxone (0.1, 0.5, 1, and 5mg/kg) on the anticonvulsant effect of tramadol were investigated. Administration of tramadol (1mg/kg) increased the threshold for seizures induced with PTZ in a monophasic, dose-independent, and time-dependent manner. Acute administration of L-NAME (5 and 10mg/kg) inhibited the anticonvulsant effect of tramadol (1mg/kg), whereas L-arginine, in the noneffective dose range (30 and 60 mg/kg), potentiated the seizure threshold when co-administered with a subeffective dose of tramadol (0.5mg/kg). Naloxone partially and dose-independently antagonized the anticonvulsant effect of tramadol (1mg/kg). These results indicate that the anticonvulsant effect of tramadol is mediated by the nitric oxide pathway and also by classic opioid receptors.
在本研究中，评估了曲马多对戊四氮（PTZ）诱导的癫痫发作的影响及其与一氧化氮（NO）的关系。为了确定强直-阵挛性癫痫发作的阈值，静脉给予 PTZ。曲马多在诱导癫痫发作前 30 分钟腹腔内给药（0.5-50mg/kg）。测定了一氧化氮合酶（NOS）抑制剂 N(G)-硝基-L-精氨酸甲酯（L-NAME；0.5、1、5 和 10mg/kg）、NO 前体 L-精氨酸（10、30 和 60mg/kg）和非特异性阿片受体拮抗剂纳洛酮（0.1、0.5、1 和 5mg/kg）对曲马多抗惊厥作用的影响。曲马多（1mg/kg）以单相、剂量非依赖性和时间依赖性方式增加 PTZ 诱导的癫痫发作的阈值。急性给予 L-NAME（5 和 10mg/kg）抑制曲马多（1mg/kg）的抗惊厥作用，而 L-精氨酸在无效剂量范围内（30 和 60mg/kg）与亚有效剂量的曲马多（0.5mg/kg）合用增强了惊厥阈值。纳洛酮部分且剂量非依赖性拮抗曲马多（1mg/kg）的抗惊厥作用。这些结果表明，曲马多的抗惊厥作用是通过一氧化氮途径介导的，也是通过经典阿片受体介导的。
