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 Gprotein 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 neurotoxicity 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 mechanism of action of guanine-based purines are still lacking, their anticonvulsant activity is probably related to the modulation of several glutamatergic parameters, especially the astrocytic glutamate uptake. These findings point to the guaninebased purines as potential new targets for the development of novel drugs for neuroprotection and management of epilepsy.