Characterization of the Effects of Phosphodiesterases (PDEs) Isozyme Inhibitors in Animal Models of Epilepsy

Epilepsy is a neurological disorder. Phosphodiesterase (PDE) enzymes are responsible for the hydrolysis of the cyclic nucleotides and therefore have a critical role in regulating intracellular levels of the second messengers cAMP, cGMP, and hence cell function as well as downstream signaling in the various body systems This study was conducted to evaluate the effect of phosphodiesterase isozymes 3, 4 and 5 inhibitors on the maximal electroshock and isoniazid induced convulsions. The results of this study suggested that zonisamide and gabapentin are anticonvulsant drugs were able to attenuate both the MES and isoniazid induced chemical convulsion respectively. On the other hand, PDE 4 inhibitor rolipram and PDE 5 inhibitor, sildenafil was actually potentiating the convulsive phenomenon that the onset of epileptic threshold was reduced as tested by MES and isoniazid induced convulsions. These studies ascertain the action of PDE-3, 4 and 5 inhibitors such as cilostazol, rolipram and sildenafil against MES induced seizures in mice. In which sildenafil (5 mg/kg, i.p.) produced a reduction in the tonic limb flexion significantly (p<0.01) when compared to other groups. Like wise, rolipram (2.4 mg/kg, i.p.) treated animals showed significant (p<0.05) reduction in tonic limb flexion. In the similar manner, sildenafil produced a reduction in the tonic extensor, clonus and stupor phases of convulsion significantly (p<0.01) when compared to other groups and the action of PDE-3, 4 and 5 inhibitors on Isoniazid (INH) induced seizures in mice. Sildenafil (5 mg/kg, i.p.) showed a gradual reduction in the onset of action, jerky movements and convulsion significantly (p<0.01) when compared to other PDE inhibitors. The PDE-3, 4 and 5 inhibitors against MES induced seizures in rats. In which sildenafil (3.5 mg/kg, i.p.) produced a gradual reduction in the tonic limb flexion significantly (p<0.01) when compared to other groups. Similarly, sildenafil produced a gradual reduction in the tonic extensor, clonus and stupor phases of convulsion significantly (p<0.01) when compared to other groups except cilostazol (7 mg/kg, i.p.) treated rats. This study concludes that PDE-5 inhibitor, sildenafil having strong proconvulsant activity in MES and INH induced animal models of epilepsy.