The effect of drugs from the class of cardiac (methyldigoxin, verapamil, propranolol), antiepileptic (carbamazepine), sedative (diazepam) and antihistaminic (promethazine) drugs on Na+, K+-ATPase activity of plasma membranes in rat brain synaptosomes was studied. Methyldigoxin in concentration of 0.1 mmol L-1 inhibits enzyme activity by 80%. Verapamil, propranolol and promethazine in concentrations of 20, 20 and 2 mmol L-1, respectively, inhibit entirely this ATPase activity. Carbamazepine and diazepam in concentrations of 0.02-60 mmol L-1 have no effect on the activity of this enzyme. According to drugs concentrations that inhibit 50% of enzyme activity (IC50), the potency order of drugs was: methyldigoxin >> promethazine > verapamil => propranolol. From inhibition of commercially available purified Na+, K+-ATPase isolated from porcine cerebral cortex in the presence of chosen drugs, as well as from the kinetic studies on synaptosomal plasma membranes, we may concluded that the drugs inhibit enzyme activity, in partly by acting directly on the enzyme protein. Propranolol, verapamil and promethazine inhibitions were in an uncompetitive manner. The results suggest that these three drugs may contribute to neurological dysfunction and point out to the necessity to take into consideration the side effects of the investigated drugs during the treatment of various pathological conditions.
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Z.I.A. AL-Fifi, 2006. Effect of Drugs from the Class of Cardiac on the Na+, K+-ATPase Activity. Journal of Biological Sciences, 6: 968-977.
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