An active metabolite of carbamazepine, carbamazepine-10,11-epoxide, inhibits ion channel-mediated catecholamine secretion in cultured bovine adrenal medullary cells

Abstract

 We have recently reported inhibitory effects of carbamazepine (CBZ) on ion channel-mediated secretion of catecholamines in bovine adrenal medullary cells. Here, we report the effects of carbamazepine-10,11-epoxide (CBZ-E), an active metabolite of CBZ, and carbamazepine-10,11-diol (CBZ-D), a non-active metabolite, on ²²Na⁺ influx, ⁴⁵Ca²⁺ influx and catecholamine secretion in cultured adrenal medullary cells. CBZ-E, but not CBZ-D inhibited ²²Na⁺ influx, ⁴⁵Ca²⁺ influx and catecholamine secretion induced by carbachol or veratridine with a half-maximal inhibitory concentration (IC₅₀) of 0.26 or 0.68 μg/ml, respectively. CBZ-E also inhibited high K⁺-evoked ⁴⁵Ca²⁺ influx and catecholamine secretion (IC₅₀ = 0.3 μg/ml), but CBZ-D did not. These findings suggest that CBZ-E, but not CBZ-D, attenuates catecholamine secretion by inhibiting nicotinic acetylcholine receptor-associated ion channels, voltage-dependent Na⁺ channels and voltage-dependent Ca²⁺ channels in the cells. This inhibition of CBZ-E as well as CBZ may be related to the clinical effects in neuropsychiatric disorders.