An active metabolite of carbamazepine, carbamazepine-10,11-epoxide, inhibits ion channel-mediated catecholamine secretion in cultured bovine adrenal medullary cells.
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.
Yoshimura
R
R
Department of Psychiatry, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Yanagihara
N
N
Terao
T
T
Minami
K
K
Toyohira
Y
Y
Ueno
S
S
Uezono
Y
Y
Abe
K
K
Izumi
F
F
D000313:Adrenal Medulla / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001569:Benzodiazepines; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D018679:Cholinergic Agonists / Q000494:pharmacology; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D012964:Sodium / Q000378:metabolism
D014151:Anti-Anxiety Agents; D002395:Catecholamines; D018679:Cholinergic Agonists; D007473:Ion Channels; D001569:Benzodiazepines; D002220:Carbamazepine; D002217:Carbachol; D012964:Sodium; C012227:carbamazepine epoxide; D002118:Calcium