Referenced in: none

Automatically associated channels: Kir2.1 , Kir3.1 , Kv11.1

Title: Blockade by NIP-142, an antiarrhythmic agent, of carbachol-induced atrial action potential shortening and GIRK1/4 channel.

Authors: Tomoyuki Matsuda, Mie Ito, Sayoko Ishimaru, Noriko Tsuruoka, Tomoaki Saito, Naoko Iida-Tanaka, Norio Hashimoto, Toru Yamashita, Nobutomo Tsuruzoe, Hikaru Tanaka, Koki Shigenobu

Journal, date & volume: J. Pharmacol. Sci., 2006 Aug , 101, 303-10

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/16891768

Abstract
Mechanisms for the atria-specific action potential-prolonging action of NIP-142 ((3R*,4S*)-4-cyclopropylamino-3,4-dihydro-2,2-dimethyl-6-(4-methoxyphenylacetylamino)-7-nitro-2H-1-benzopyran-3-ol), a benzopyran compound that terminates experimental atrial arrhythmia, was examined. In isolated guinea-pig atrial tissue, NIP-142 reversed the shortening of action potential duration induced by either carbachol or adenosine. These effects were mimicked by tertiapin, but not by E-4031. NIP-142 concentration-dependently blocked the human G protein-coupled inwardly rectifying potassium channel current (GIRK1/4 channel current) expressed in HEK-293 cells with an EC50 value of 0.64 microM. At higher concentrations, NIP-142 blocked the human ether a go-go related gene (HERG) channel current with an EC50 value of 44 microM. In isolated guinea-pig papillary muscles, NIP-142 had no effect on the negative inotropic effect of carbachol under beta-adrenergic stimulation, indicating lack of effect on the muscarinic receptor and Gi protein. These results suggest that NIP-142 directly inhibits the acetylcholine-activated potassium current.