Ivermectin (IVM) is an antiparasitic drug that primarily works by the activation of GABA_A receptors. The potential pharmacological pathways behind the anti-convulsant effect of IVM haven’t yet been identified. In this study, intravenous injection of pentylenetetrazole (PTZ)-induced clonic seizure in mice was investigated in order to assess the possible influence of IVM on clonic seizure threshold (CST). We also look at the function of the Opioidergic and nitrergic pathways in IVM anticonvulsant action on clonic seizure threshold. IVM (0.5, 1, 5, and 10 mg/kg, i.p.) raised the PTZ-induced CST, according to our findings. Furthermore, the ineffective dose of nitric oxide synthase inhibitors (L-NAME 10 mg/kg, i.p.), and (7-NI 30 mg/kg, i.p.) or opioidergic system agonist (morphine 0.25 mg/kg, i.p.) were able to amplify the anticonvulsive action of IVM (0.2 mg/kg, i.p.). Moreover, the anticonvulsant effect of IVM was reversed by an opioid receptor antagonist (naltrexone 1 mg/kg, i.p.). Furthermore, the combination of the ineffective dose of morphine as an opioid receptor agonist with either L-NAME (2 mg/kg, i.p.) or 7-NI (10 mg/kg, i.p.) and with an ineffective dose of IVM (0.2 mg/kg, i.p.) had a significant anticonvulsant effect. Taken together, IVM has anticonvulsant activity against PTZ-induced clonic seizures in mice, which may be mediated at least in part through the interaction of the opioidergic system and the nitric oxide pathway.

伊维菌素 (IVM) 是一种抗寄生虫药，主要通过激活 GABA _A起作用受体。IVM 抗惊厥作用背后的潜在药理学途径尚未确定。在这项研究中，研究了静脉注射戊四唑 (PTZ) 诱导的小鼠阵挛发作，以评估 IVM 对阵挛发作阈值 (CST) 的可能影响。我们还研究了阿片能和氮能通路在 IVM 抗惊厥作用中对阵挛发作阈值的作用。根据我们的研究结果，IVM（0.5、1、5 和 10 mg/kg，ip）提高了 PTZ 诱导的 CST。此外，无效剂量的一氧化氮合酶抑制剂（L-NAME 10 mg/kg，ip）和（7-NI 30 mg/kg，ip）或阿片能系统激动剂（吗啡 0.25 mg/kg，ip）能够增强 IVM (0.2 mg/kg, ip) 的抗惊厥作用。而且，IVM 的抗惊厥作用被阿片受体拮抗剂（纳曲酮 1 mg/kg，腹腔注射）逆转。此外，无效剂量的吗啡作为阿片受体激动剂与 L-NAME（2 mg/kg，ip）或 7-NI（10 mg/kg，ip）以及无效剂量的 IVM（0.2 mg /kg, ip)具有显着的抗惊厥作用。总之，IVM 对 PTZ 诱导的小鼠阵挛发作具有抗惊厥活性，这可能至少部分是通过阿片能系统和一氧化氮途径的相互作用介导的。)有显着的抗惊厥作用。总之，IVM 对 PTZ 诱导的小鼠阵挛发作具有抗惊厥活性，这可能至少部分是通过阿片能系统和一氧化氮途径的相互作用介导的。)有显着的抗惊厥作用。总之，IVM 对 PTZ 诱导的小鼠阵挛发作具有抗惊厥活性，这可能至少部分是通过阿片能系统和一氧化氮途径的相互作用介导的。