Role of Adenylate Cyclase Guanylate Cyclase Enzyme and Phosphodiesterase Isozyme Modulation in Animal Models of Epilepsy

Abstract

Epilepsy is a generally a chronic neurological disorder. Neither an effective prophylaxsis nor a permanent cure of any of these disorders is available except neurosurgical resection of epileptic tissue in selected instances. There is hope that understanding the cellular and molecular mechanisms of the epilepsies will lead to improved therapies as well as new insights into brain structure and function. Because of the inherent diversity of the epilepsies and their models and the wide range of techniques used for investigating their cellular and molecular basis, I had focused on selected models and issues, attempted to bring some coherency to the findings, and sought to draw conclusions that may be generally relevant to epilepsy. I made a special effort to show how investigations of the epilepsies with methods from diverse disciplines can be complementary and mutually reinforcing. By use of the tools of electrophysiology it was initially demonstrated that the epilepsies are disorders of neuronal excitability, which were subsequently characterized in populations of neurons, in individual neurons, and single ion channels. Finally, I present ways of utilizing PDE inhibitors for the study of epilepsy in animals. The data explains that methylene blue alone, methylene blue with BRL50481 greatly increased the anti-convulsant activity along with higher protection range of animals were seen in both models. The combination of A- 350619 with BRL50481 as well as the individual effect of A-350619 and BRL 50481 alone showed a quick onset of seizures response with increased the mortality range in both animal models of epilepsy. The combination of sGC inhibitor, methylene blue with etazolate showed a delay onset of seizures, compared to other groups. This confirms that sGC inhibitor having anti-convulsant activity. The study also demonstrates that etazolate alone and etazolate in combination with BRL50481 greatly enhances quick onset of seizures. So, this study strongly suggests that etazolate having proconvulsant activity.