J Nandhakumar, Vinita Ernest and Manoj G Tyagi
The role of soluble guanylate cyclase (GC) activator (A-350619) and inhibitor (methylene blue) was evaluated in the presence of phosphodiesterase-7 (PDE-7) inhibitor such as BRL-50481, in animal models of epilepsy. Seizures were induced in the animals by subjecting them to an injection of chemical convulsant, pentylenetetrazole (PTZ) and maximal electroshock (MES). The study mainly comprises the onset of seizures, mortality/recovery, percentage of prevention of seizures (anti-convulsant) and total duration of convulsive time. The combination of GC inhibitor, methylene blue with BRL 50481 showed a delay onset (P<0.001) in incidence of seizures, compared to A-350619 and BRL 50481 alone treated group. The total convulsive time was prolonged significantly (P<0.01) in methylene blue alone treated (69.2%) groups, compared to DMSO received group (100%). The study also demonstrates that methylene blue alone and methylene blue with BRL 50481 greatly increased the anti-convulsant activity (P<0.01 and P<0.05) along with higher protection 83.3% and 66.7% range respectively in PTZ model. Methylene blue with BRL 50481 effectively (P<0.01) decreased the MES (150 mA, 0.2 sec) induced convulsion, compared to DMSO. The data shows that methylene blue alone, methylene blue with BRL 50481 greatly increased the anti-convulsant activity (P<0.01 and P<0.01) along with higher protection 83.3% range in animals treated with MES. The present result suggested of the possible involvement of methylene blue alone and with presence of BRL 50481, delays the onset of seizure activity as well as prolongs the total duration of convulsive time in both models.