Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016;14(7):759-71.
doi: 10.2174/1570159x14666160603115942.

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

Joaquín Manjarrez-Marmolejo, Javier Franco-Pérez  1
Affiliations
Review

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

Joaquín Manjarrez-Marmolejo et al. Curr Neuropharmacol. 2016.

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.

PubMed Disclaimer

Figures

Fig. (1)
Fig. (1)
Percentage of rats with Tonic Hindlimb Extension (THLE) and duration of THLE after the application of maximal electroshock in rats previously administered with saline solution (negative control), valproic acid (positive control) and with different doses of Carbenoxolone (CBX) (1A, 1E), Quinine (QUIN) (1B, 1F), Mefloquine (MFQ) (1C, 1G) and Quinidine (QND) (1D, 1H). Values are expressed as a percentage and in seconds (mean ± SEM). The level of significance for percentage of rats with THLE was determined by independent Fisher´s exact probability tests comparing each experimental group versus saline group The level of significance for duration of THLE was determined by a Kruskal-Wallis one-way analysis of variance on ranks (*p<0.05).
Fig. (2)
Fig. (2)
The intraperitoneal administration of mefloquine (40 mg/kg) inhibits the epileptiform activity induced by the application of pentylenetetrazole (70 mg/kg) in rats.
See this image and copyright information in PMC

References

    1. Furshpan E.J., Potter D.D. Transmission at the giant motor synapses of the crayfish. J. Physiol. 1959;145(2):289–325. [http:// dx.doi.org/10.1113/jphysiol.1959.sp006143]. [PMID: 13642302]. - PMC - PubMed
    1. Connors B.W., Long M.A. Electrical synapses in the mammalian brain. Annu. Rev. Neurosci. 2004;27:393–418. [http://dx.doi.org/ 10.1146/annurev.neuro.26.041002.131128]. [PMID: 15217338]. - PubMed
    1. Pereda A.E. Electrical synapses and their functional interactions with chemical synapses. Nat. Rev. Neurosci. 2014;15(4):250–263. [http://dx.doi.org/10.1038/nrn3708]. [PMID: 24619342]. - PMC - PubMed
    1. Willecke K., Eiberger J., Degen J., Eckardt D., Romualdi A., Güldenagel M., Deutsch U., Söhl G. Structural and functional diversity of connexin genes in the mouse and human genome. Biol. Chem. 2002;383(5):725–737. [http://dx.doi.org/10.1515/BC. 2002.076]. [PMID: 12108537]. - PubMed
    1. Söhl G., Willecke K. Gap junctions and the connexin protein family. Cardiovasc. Res. 2004;62(2):228–232. [http://dx.doi.org/ 10.1016/j.cardiores.2003.11.013]. [PMID: 15094343]. - PubMed

Substances