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

Article Details

Citation
Copy to clipboard

Yoshimura R, Yanagihara N, Terao T, Minami K, Toyohira Y, Ueno S, Uezono Y, Abe K, Izumi F

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

Psychopharmacology (Berl). 1998 Feb;135(4):368-73.

PubMed ID
9539261 [ View in PubMed
]
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 microg/ml, respectively. CBZ-E also inhibited high K+-evoked 45Ca2+ influx and catecholamine secretion (IC50 = 0.3 microg/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.

DrugBank Data that Cites this Article

Drugs