Inhibition of cyclic adenosine 3‘,5‘–monophosphate (cAMP) in the generation of seizure threshold by potent specific phosphodiesterase (PDE–3) inhibitors

Dr.B.Prathap; Dr.E.Seshathri; Dr.P.Jacob Verghese; Dr. J. Nandhakumar

Volume : X, Issue : II, February - 2020

Inhibition of cyclic adenosine 3‘,5‘–monophosphate (cAMP) in the generation of seizure threshold by potent specific phosphodiesterase (PDE–3) inhibitors

Dr. B. Prathap, Dr. E. Seshathri, Dr. P. Jacob Verghese, Dr. J. Nandhakumar

Abstract :

Objective: To investigate the role of specific phosphodiesterase (PDE–3) inhibitors like cilostazol and milrinone with the cellular level accumulation of cAMP in the generation of seizures. Materials & Methods: Generation of seizures were carried out in the animals by subjecting them to injection of chemical convulsants like pentylenetetrazole (PTZ) at the dose of 60 mg/kg, i.p and Isoniazid (INH) at the dose of 300mg/kg, s.c and by maximal electroshock (MES) at 45 mA for 0.2 sec. The animals were pre–treated with various dose levels of cilostazol (0.5 mg/kg, 0.6 mg/kg and 0.7 mg/kg) and milrinone (50 μg/kg, 100 μg/kg, 200 μg/kg, 300 μg/kg) 15 mins prior to the PTZ, INH and MES. The control animals received normal saline (5 ml/kg, i.p) 15 mins prior to the injection of PTZ and INH (or) MES. Results: PDE–3 inhibitors significantly enhanced the onset of seizures induced by PTZ, INH and MES. In particularly milrinone potentiated the convulsive phenomenon more significantly (p < 0.05 and p < 0.001) when compare with cilostazol. Conclusion: This study demonstrates the vital role of specific PDE–3 inhibitors like cilostazol and milrinone in the generation of seizure threshold through the increased cellular concentration cAMP results in the activation of protein kinase A and its phosphorylation processes.