Anticonvulsant activity of gap-junctional blocker carbenoxolone in albino rats

Background: Gap junctions (GJs) are clusters of channels that connect the interiors of adjoining neurons and mediate electrical/electrotonic coupling by transfer of ions and small molecules. Electrotonic coupling between principal neurons via GJs is increasingly recognized as one of the mechanisms in the pathogenesis of the abnormal neuronal synchrony that occurs during seizures. Carbenoxolone the succinyl ester of glycyrrhetinic acid obtained from liquorice has been shown to have the property of blocking gap junctional intercellular communication. The objectives were to study if carbenoxolone has in-vivo anticonvulsive activity in pentylenetetrazole (PTZ) and maximal electroshock (MES) seizure models and to probe the functional role of GJs in seizures. Methods: Carbenoxolone was tested for anticonvulsive effect in albino rats subjected to seizures by the PTZ and MES at three doses 100 m/kg, 200 m/kg, 300 m/kg. In the PTZ model parameters observed were seizure protection, seizure latency and seizure duration. In the MES model parameters observed were seizure protection and seizure duration. Results: The results showed that the carbenoxolone has anticonvulsant activity in both PTZ and MES induced seizures with better protection in the PTZ induced seizures. In the PTZ model carbenoxolone produced a statistically significant increase in seizure latency, decrease in seizure duration and seizure protection. In the MES model carbenoxolone produced a statistically significant decrease in seizure duration. Conclusions: Carbenoxolone has in-vivo anticonvulsive effect and could be useful in both petitmal (absence) seizures and grand mal (generalized tonic-clonic epilepsy) seizures. The protective effect of carbenoxolone could be due to blockade of GJ channels that mediate electro tonic coupling and thereby prevent the neural synchronization that is characteristic of seizures. The study also supports the view that GJs have a functional role in the electrophysiology of seizures and GJ blockers have potential as a new class of antiepileptic drugs.