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.