A novel benzopyran derivative NIP-142 has unique atrium- and sinus-selective antiarrhythmic effects in vitro

• Published in: Japanese Journal of Pharmacology Vol. 79; no. suppl.1; p. 176
• Main Authors: Toru Yamashita, Tomoyuki Matsuda, Maho Itokawa, Hikaru Tanaka, Koki Shigenobu, Nobutomo Tsuruzoe
• Format: Journal Article
• Language: Japanese
• Published: The Japanese Pharmacological Society 1999
• ISSN: 0021-5198; 1347-3506

NIP-142 (NIP) is a newly synthesized benzopyran derivative showing bradycardiac and unique antiarrhythmic effects. In the present study, pharmacological properties of NIP were examined using isolated guinea-pig cardiac tissues. NIP (>1μM) decreased, in a concentration-dependent manner, the spontaneous beating rate of right atria. This negative chronotropic effect was about five times larger than the negative inotropism observed in right ventricular papillary muscles. NIP (10μM) completely terminated aconitine-induced arrhythmia in atrium but not in ventricle. NIP selectively prolonged functional refractory period in atrium but not in ventricle. It was also found that NIP bound to batrachotoxin-sensitive Na^+ channel site 2 receptor to which aconitine is known to bind, whereas NIP did not bind to TTX-sensitive Na^+ channel site 1 receptor. These findings suggest that NIP may be a new type of antiarrhythmic drug, especially for sinus tachycardia and atrial fibrillation /flutter.