title: Effects of meclofenamic acid on limbic epileptogenesis in mice kindling models.
abstract: The most avid goal for antiepileptic drugs (AEDs) development today is to discover potential agents to prevent epilepsy or slow the process of epileptogenesis. Accumulating evidence reveals that gap junctions in the brain may be involved in epileptogenesis. Meclofenamic acid (MFA), a gap junction blocker, has not yet been applied in epileptogenic models to test whether it has antiepileptogenic or disease-modifying properties or not. In this study, we investigated the effects of MFA on limbic epileptogenesis in amygdaloid kindling and hippocampus rapid kindling models in mice. We found that intracerebroventricular (i.c.v., 2 μl) administration of either dose of MFA (100 μM, 1mM or 100mM) 15 min prior daily kindling stimulus decreased seizure stage, shortened the after-discharge duration (ADD) and increased the number of stimulations required to elicit stage 5 seizure. MFA also prevented the establishment of post-kindling enhanced amygdala excitability, evident as the increase of afterdischarge threshold (ADT) compared with pre-kindling values. Furthermore, MFA retarded kindling acquisition in mice hippocampus rapid kindling model as well, which demonstrated that the antiepileptogenic effects of MFA were not specific to the amygdala but also occur in other limbic structures such as the hippocampus. Our results confirm that MFA can slow the limbic epileptogenesis in both amygdaloid kindling and hippocampus rapid kindling models, and indicate that MFA may be a potential drug that has antiepileptogenic or disease-modifying properties.
authors.affiliation: Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China and Zhejiang Province Key Laboratory of Neurobiology, College of Pharmaceutical Sciences, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Jin
authors.forename: Yunjian
authors.initials: Y
authors.lastname: Dai
authors.forename: Cenglin
authors.initials: C
authors.lastname: Xu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D004558:Electric Stimulation; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D057967:Infusions, Intraventricular; D007696:Kindling, Neurologic / Q000187:drug effects*; D008032:Limbic System / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000927:Anticonvulsants; D008469:Meclofenamic Acid