Abstract
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.
Highlights
Epilepsy is a serious neurological disorder that affects a wide range of people throughout the world
The combination of methylene blue and PDE-7 inhibitor, BRL 50481 received mice showed a significant (P
The data obtained from this study shown that pre-treatment with soluble guanylate cyclase inhibitor, methylene blue alone and with the PDE-7 inhibitor such as BRL 50481, potentiates the anti-convulsant activity against the PTZ and Maximal electroshock (MES) induced convulsions as described in Table 1 & 2
Summary
Epilepsy is a serious neurological disorder that affects a wide range of people throughout the world. It is a disorder of brain characterized by unpredictable and periodic occurrence of a transient alteration of behaviour due to the disordered, synchronous and rhythmic firing of populations of brain neurons [1]. It has been observed that the presently available anti-epileptic drugs are unable to control seizures effectively in as many as 25% of the patients [3]. The conventional anti-epileptic agents like phenytoin, carbamazeipine and sodium valporate carry with them several serious side effects notably neurotoxicity [4]. Newer anti-epileptics like gabapentin, vigabatrin, lamotrigine, etc., are used supplemental to the conventional agents [1]
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