Evaluation of cyclic nucleotide phosphodiesterase III inhibitors in animal models of epilepsy

This study was conducted to investigate the role of specific phosphodiesterase-3 (PDE-3) inhibitors like amrinone and milrinone in the generation of seizures in albino Swiss mice. Generation of seizures were carried out in the animals by subjecting them to injection of a chemical convulsant, isoniazid (INH) at the dose of 500mg/kg, s.c and by subjecting them to maximal electroshock (MES) at 60 mA for 0.2 sec. The animals were pre-treated with various dose levels of amrinone (0.5 mg/kg, 0.6 mg/kg and 0.7 mg/kg, i.p) and milrinone (50μg/kg, 100 μg/kg, 200μg/kg, 300 μg/kg, i.p) 20 mins prior to the INH or MES. The control group of animals received normal saline (5 ml/kg i.p) 20 mins prior to the injection of INH , or before subjecting the animals to MES. PDE-3 inhibitors significantly enhanced the onset of seizures induced by INH and MES. In particular, milrinone potentiated the convulsive phenomenon more significantly (p<0.05 and p< 0.001) when compared with amrinone.