SD-3212, a new class I and IV antiarrhythmic drug: a potent inhibitor of the muscarinic acetylcholine-receptor-operated potassium current in guinea-pig atrial cells

British Journal of Pharmacology
Y Hara, H Nakaya

Abstract

1. By use of patch-clamp techniques, the effects of SD-3212, a novel antiarrhythmic drug, on the calcium current (Ica), the sodium current (INa) and the muscarinic acetylcholine-receptor-operated potassium current (IK.ACh) were examined and compared with those of bepridil in guinea-pig single atrial cells. 2. SD-3212 inhibited ICa and INa in a concentration-dependent manner. The IC50 values of SD-3212 for inhibition of ICa and INa were 1.29 microM and 3.92 microM, respectively. The steady state inactivation curves of ICa and INa were shifted in the hyperpolarizing direction in the presence of 1 microM SD-3212. Similar inhibition of ICa and INa was also observed with bepridil. The IC50 values of bepridil for depression of ICa and INa were 1.55 microM and 4.43 microM, respectively. 3. The muscarinic acetylcholine-receptor-operated potassium current (IK.ACh) was activated by the extracellular application of 1 microM carbachol in the GTP-loaded cells or by the intracellular loading of GTP gamma S, a nonhydrolysable GTP analogue. SD-3212 potently inhibited the carbachol- and GTP gamma S-induced IK.ACh and the IC50 values were 0.38 microM and 0.20 microM, respectively. These IC50 values were very close and about 10 times lower than t...Continue Reading

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Citations

Nov 17, 2001·European Journal of Pharmacology·S KobayashiH Nakaya
Jan 4, 1998·European Journal of Pharmacology·Y WatanabeH Nakaya
Dec 15, 2005·Heart, Lung & Circulation·Yukio Hara, Keiichiro Kizaki
Oct 3, 2012·European Journal of Pharmacology·Sayuri SuzukiIchiro Hisatome
Aug 14, 2003·The American Journal of Cardiology·Akira FujikiHiroshi Inoue
Feb 2, 2013·Biological & Pharmaceutical Bulletin·Akira TakaharaHikaru Tanaka
Jan 7, 2005·Circulation Journal : Official Journal of the Japanese Circulation Society·Yuji NakazatoHiroyuki Daida
Feb 3, 2007·Internal Medicine·Daisuke IzumiYoshifusa Aizawa
Jun 5, 2001·Japanese Journal of Pharmacology·Y Watanabe, J Kimura
Sep 23, 2006·Journal of Pharmacological Sciences·Yasuhide WatanabeJunko Kimura
Dec 6, 2007·Circulation Journal : Official Journal of the Japanese Circulation Society·Akira Fujiki, Hiroshi Inoue
Aug 7, 2007·The Journal of Veterinary Medical Science·Yukio HaraKeiichiro Kizaki
May 27, 2008·Circulation Journal : Official Journal of the Japanese Circulation Society·Tomomichi IshizakaAtsushi Sugiyama
May 21, 1998·The Journal of Veterinary Medical Science·Y HaraH Kondo
Mar 22, 2001·The Journal of Veterinary Medical Science·Y HaraH Kondo
Sep 12, 2007·Expert Opinion on Therapeutic Targets·Deepak Bhakta, John M Miller
Jun 1, 1997·Journal of Pharmaceutical and Biomedical Analysis·M E Rodriguez RosasT Nakagawa

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