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Gap Junction Blockers: An Overview of their Effects on Induced Seizures in Animal Models

[ Vol. 14 , Issue. 7 ]

Author(s):

Joaquín Manjarrez-Marmolejo and Javier Franco-Pérez   Pages 759 - 771 ( 13 )

Abstract:


Background: Gap junctions are clusters of intercellular channels allowing the bidirectional pass of ions directly into the cytoplasm of adjacent cells. Electrical coupling mediated by gap junctions plays a role in the generation of highly synchronized electrical activity. The hypersynchronous neuronal activity is a distinctive characteristic of convulsive events. Therefore, it has been postulated that enhanced gap junctional communication is an underlying mechanism involved in the generation and maintenance of seizures. There are some chemical compounds characterized as gap junction blockers because of their ability to disrupt the gap junctional intercellular communication.

Objective: Hence, the aim of this review is to analyze the available data concerning the effects of gap junction blockers specifically in seizure models.

Results: Carbenoxolone, quinine, mefloquine, quinidine, anandamide, oleamide, heptanol, octanol, meclofenamic acid, niflumic acid, flufenamic acid, glycyrrhetinic acid and retinoic acid have all been evaluated on animal seizure models. In vitro, these compounds share anticonvulsant effects typically characterized by the reduction of both amplitude and frequency of the epileptiform activity induced in brain slices. In vivo, gap junction blockers modify the behavioral parameters related to seizures induced by 4-aminopyridine, pentylenetetrazole, pilocarpine, penicillin and maximal electroshock.

Conclusion: Although more studies are still required, these molecules could be a promising avenue in the search for new pharmaceutical alternatives for the treatment of epilepsy.

Keywords:

Anticonvulsant drugs, carbenoxolone, connexins, gap junctions, mefloquine, quinidine, quinine, seizures.

Affiliation:

Laboratory of Physiology of Reticular Formation, National Institute of Neurology and Neurosurgery, M.V.S. Insurgentes Sur 3877, Col. La Fama, C.P. 14269, Mexico D.F., Mexico.

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