Effect of carbamazepine on the in vitro uptake and release of norepinephrine in adrenergic nerves of rabbit aorta and in whole brain synaptosomes.

The effects of carbamazepine, in vitro, on adrenergic neuronal and whole brain synaptosomal uptake and release of tritiated norepinephrine (3H-NE) were assessed. At 10(-4) M, carbamazepine inhibited 3H-NE uptake by 22% in rabbit thoracic aorta and in brain synaptosomes. At the same concentration, carbamazepine inhibited stimulation-induced release of 3H-NE by 42.6% and inhibited isometric contraction in rabbit ear artery helical strips by 31.6%. At 10(-5) M, carbamazepine exhibited a 17.6% inhibition of 3H-NE uptake in brain synaptosomes in the absence of effects on transmitter release. Cocaine, 10(-4) M, and imipramine, 10(-4) M, inhibited uptake by 88% and 85%, respectively, in aorta, and cocaine, 10(-4) M, inhibited synaptosomal uptake by 67.7%. Since antiepileptic blood levels of carbamazepine range between 1.3 and 3.0 X 10(-5) M, it was concluded that the observed effects of carbamazepine are insufficient to account for the anticonvulsant action of the drug. However, the blockade of 3H-NE uptake by brain synaptosomes at 10(-5) M serves to explain the recently described analeptic activity of this agent.