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.


Keywords


PDE-3 inhibitors, cAMP, Cilostazol, Milrinone, Seizures.

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