The Role of the Guanine-Based Purinergic System in Seizures and Epilepsy

Guanine-based purines have been traditionally studied as modulators of intracellular processes, mainly G- protein activity. However, more recently, several studies have shown that they exert a variety of extracellular effects not related to G-proteins, including trophic effects on neural cells, modulation of glutamatergic activity, behavioral effects and anticonvulsant activity. In this article, the putative effects of the guanine-based purines against seizures and neurotox- icity are reviewed. Current evidence suggests that guanine-based purines, especially guanosine, seem to be endogenous anticonvulsant substances, perhaps in a similar way to the adenine-based purines. Although studies addressing the mecha- nism of action of guanine-based purines are still lacking, their anticonvulsant activity is probably related to the modula- tion of several glutamatergic parameters, especially the astrocytic glutamate uptake. These findings point to the guanine- based purines as potential new targets for the development of novel drugs for neuroprotection and management of epi- lepsy.