title: Effect of carbamazepine on the in vitro uptake and release of norepinephrine in adrenergic nerves of rabbit aorta and in whole brain synaptosomes.
abstract: 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.
mesh_terms: D000320:Adrenergic Fibers / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D002220:Carbamazepine / Q000494:pharmacology*; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000378:metabolism*; D011817:Rabbits; D009435:Synaptic Transmission / Q000187:drug effects*; D013574:Synaptosomes / Q000378:metabolism
chemical_list: D002220:Carbamazepine; D009638:Norepinephrine