Amini-Khoei Hossein, Kordjazy Nastaran, Haj-Mirzaian Arvin, Amiri Shayan, Haj-Mirzaian Arya, Shirzadian Armin, Hasanvand Amin, Balali-Dehkordi Shima, Hassanipour Mahsa, Dehpour Ahmad Reza
a Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran.
b Department of Physiology and Pharmacology, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Can J Physiol Pharmacol. 2018 Aug;96(8):742-750. doi: 10.1139/cjpp-2017-0673. Epub 2018 Mar 20.
Anticonvulsant effects of minocycline have been explored recently. This study was designed to examine the anticonvulsant effect of acute administration of minocycline on pentylenetetrazole-induced seizures in mouse considering the possible role of the nitric oxide/N-methyl-d-aspartate (NMDA) pathway. We induced seizure using intravenous administration of pentylenetetrazole. Our results showed that acute administration of minocycline increased the seizure threshold. Furthermore, co-administration of subeffective doses of the nonselective nitric oxide synthase (NOS) inhibitor N-l-arginine methyl ester (10 mg/kg) and the neuronal NOS inhibitor 7-nitroindazole (40 mg/kg) enhanced the anticonvulsant effect of subeffective doses of minocycline (40 mg/kg). We found that inducible NOS inhibitor aminoguanidine (100 mg/kg) had no effect on the antiseizure effect of minocycline. Moreover, l-arginine (60 mg/kg), as a NOS substrate, reduced the anticonvulsant effect of minocycline. We also demonstrated that pretreatment with the NMDA receptor antagonists ketamine (0.5 mg/kg) and MK-801 (0.05 mg/kg) increased the anticonvulsant effect of subeffective doses of minocycline. Results showed that minocycline significantly decreased the hippocampal nitrite level. Furthermore, co-administration of a neuronal NOS inhibitor like NMDA receptor antagonists augmented the effect of minocycline on the hippocampal nitrite level. In conclusion, we revealed that anticonvulsant effect of minocycline might be, at least in part, due to a decline in constitutive hippocampal nitric oxide activity as well as inhibition of NMDA receptors.
米诺环素的抗惊厥作用最近已得到研究。本研究旨在探讨急性给予米诺环素对戊四氮诱导的小鼠癫痫发作的抗惊厥作用，并考虑一氧化氮/N-甲基-D-天冬氨酸（NMDA）途径的可能作用。我们通过静脉注射戊四氮诱导癫痫发作。我们的结果表明，急性给予米诺环素可提高癫痫发作阈值。此外，联合给予亚有效剂量的非选择性一氧化氮合酶（NOS）抑制剂N-L-精氨酸甲酯（10mg/kg）和神经元NOS抑制剂7-硝基吲唑（40mg/kg）可增强亚有效剂量米诺环素（40mg/kg）的抗惊厥作用。我们发现，诱导型NOS抑制剂氨基胍（100mg/kg）对米诺环素的抗癫痫作用没有影响。此外，作为NOS底物的L-精氨酸（60mg/kg）降低了米诺环素的抗惊厥作用。我们还证明，用NMDA受体拮抗剂氯胺酮（0.5mg/kg）和MK-801（0.05mg/kg）预处理可增强亚有效剂量米诺环素的抗惊厥作用。结果表明，米诺环素显著降低了海马亚硝酸盐水平。此外，联合给予神经元NOS抑制剂如NMDA受体拮抗剂可增强米诺环素对海马亚硝酸盐水平的影响。总之，我们发现米诺环素的抗惊厥作用可能至少部分归因于海马组成型一氧化氮活性的下降以及NMDA受体的抑制。
