Kaneko Noboru, Matsuda Ryuko, Hata Yoshihito, Shimamoto Ken
Department of Cardiology and Pneumology, Dokkyo Medical University, Tochigi, Japan.
Curr Clin Pharmacol. 2009 May;4(2):126-31. doi: 10.2174/157488409788184972.
K201 is a 1,4-benzothiazepine derivative that is a promising new drug with a strong cardioprotective effect. We initially discovered K201 as an effective suppressant of sudden cardiac cell death due to calcium overload. K201 is a non-specific blocker of sodium, potassium and calcium channels, and its cardioprotective effect is more marked than those of nicorandil, prazosine, propranolol, verapamil and diltiazem. Recently, K201 has also been shown to have activities indicated for treatment of atrial fibrillation, ventricular fibrillation, heart failure and ischemic heart disease, including action as a multiple-channel blocker, inhibition of diastolic Ca(2+) release from the sarcoplasmic reticulum, suppression of spontaneous Ca(2+) sparks and Ca(2+) waves, blockage of annexin V and provision of myocardial protection, and improvement of norepinephrine-induced diastolic dysfunction. Here, we describe the pharmacological characteristics and clinical applications of K201.
K201是一种1,4 - 苯并硫氮杂䓬衍生物,是一种具有强大心脏保护作用的新型有前景药物。我们最初发现K201是一种因钙超载导致的心脏细胞猝死的有效抑制剂。K201是钠、钾和钙通道的非特异性阻滞剂,其心脏保护作用比尼可地尔、哌唑嗪、普萘洛尔、维拉帕米和地尔硫䓬更为显著。最近,K201还被证明具有用于治疗心房颤动、心室颤动、心力衰竭和缺血性心脏病的活性,包括作为多通道阻滞剂的作用、抑制肌浆网舒张期Ca(2+)释放、抑制自发性Ca(2+)火花和Ca(2+)波、阻断膜联蛋白V以及提供心肌保护,以及改善去甲肾上腺素诱导的舒张功能障碍。在此,我们描述K201的药理学特性和临床应用。