Pharmacological characteristics and clinical applications of K201.
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.
Department of Cardiology and Pneumology, Dokkyo Medical University, Tochigi, Japan. nkaneko@dokkyomed.ac.jp
Noboru
N
Kaneko
Ryuko
R
Matsuda
Yoshihito
Y
Hata
Ken
K
Shimamoto
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D006331:Heart Diseases / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013841:Thiazepines / Q000494:pharmacology*
D002316:Cardiotonic Agents; D013841:Thiazepines; C109183:K201 compound; D002118:Calcium