Inhibition of rat brain ecto-ATPase activity by various drugs

The in vitro effect of digoxin, verapamil, propranolol, carbamazepine, diazepam and promethazine were investigated on the ecto-ATPase activity of synaptosomal plasma membranes from the rat brain. ATP hydrolyzing activities of the enzyme were not affected by digoxin while the use of all other drugs resulted in significant and dose-dependent ihibition in ATP hydrolysis. According to values Of IC50 and K-iapp, the order of inhibitory potency of the drugs applied was: diazepam > promethazine > verapamil > propranolol >> carbamazepine. Kinetic analysis of the nature of the ATPase inhibition revealed that it resulted from a direct action of drugs on the enzyme protein. The aim of the present study was to determine the potential neuromodulatory side effects of the drugs investigated. The results achieved indicated that all investigated drugs, except digoxin, may modulate neuronal activities via the purinergic receptors P2 by increasing extracellular concentrations of ATP as a consequence of inhibition of the ecto-ATPase activity. Our findings indicate that it may be useful to take into consideration the possible side effects of the investigated drugs, when they are used in treatment of different pathologies, particularly in the treatment of epilepsy by carbamazepine and diazepam.