An activation of synaptosomal Na super(+),K super(+)-ATPase by a novel dibenzoxazepine derivative (BY-1949) in the rat brain: Its functional role in the neurotransmitter uptake systems

In search of factors mitigating the final outcome of ischemic and epileptic brain damage, we tested a novel dibenzoxazepine derivative (BY-1949), as the compound has been shown to be effective under these two conditions. First, using rat brain, we assessed whether or not BY-1949 affects the Na super(+),K super(+)-ATPase activity. Although in vitro applications of either BY-1949 or its three major metabolites did not cause any apparent effects, both acute and chronic oral administrations of the compound (10 mg/kg) invariably increased the Na super(+),K super(+)-ATPase activity in the synaptosomal plasma membranes by increasing V sub(max) values. Second, it was shown by this study that the drug treatment caused marked increases in the uptake of both glutamic acid and gamma -aminobutyric acid into the synaptosomes. These results suggest that the activity against ischemic/epileptic brain damage by BY-1949 is explicable, at least partly, in terms of improvement of ionic derangements across the neural membranes via Na super(+),K super(+)-ATPase activation.