Indian Journal of Science and Technology

Abstract

The role of adenylate cyclase (AC) inhibitor (SQ22536) was evaluated in the presence of PDE-5/6/8/10/11 and PDE-7 inhibitors such as dipyridamole and BRL-50481 in animal models of epilepsy. Seizures were induced in the animals by subjecting them to injection of chemical convulsant, pentylenetetrazole (PTZ) and maximal electroshock (MES). The study mainly comprises of the onset of seizures, mortality/recovery, percentage of prevention of seizures (anticonvulsant) and total duration of convulsive time. Present study mainly highlights the combined effects of AC inhibitor SQ22536 with dipyridamole as well as BRL50481 showed a good reduction (P<0.001) in incidence of seizures, compared to SQ22536 and BRL50481 alone treated mice against PTZ (60 mg/kg, i.p.) model. The total convulsive time was prolonged significantly (P<0.01) in SQ22536 alone treated (60.2%) and in with combination of SQ22536 with BRL50481 treated (27.4%) groups, compared to DMSO received group (100%). The study also demonstrates that SQ22536 alone, SQ22536 followed by dipyridamole and SQ22536 with BRL50481 greatly increased the anticonvulsant activity (P<0.01, P<0.05 and P<0.01) along with higher protection 83.3%, 66.7% and 50% range respectively. SQ22536 with dipyridamole effectively (P<0.001) decreased the MES (150 mA, 0.2 sec) induced convulsion, compared to SQ22536. The data shows that SQ22536 alone, SQ22536 followed by dipyridamole and SQ22536 with BRL50481 greatly increased the anti-convulsant activity (P<0.01, P<0.01 and P<0.01) along with higher protection 83.3%, 50% and 66.7% range respectively in animals pre-treated with MES. The results suggest the possible involvement of SQ22536 alone and with presence of dipyridamole and BRL50481, delays the onset of seizure activity as well as prolongs the total duration of convulsive time in both models.
Keywords: Adenylate cyclase, PDE, SQ22536, dipyridamole, BRL50481, seizures