[Pharmacological and clinical profile of nifekalant (shinbit injection), a class III antiarrhythmic drug].
Nifekalant (shinbit, MS-551) is a pure class III antiarrhythmic drug (Vaughan Williams' classification), which was approved in Japan in June 1999. This drug prolongs the action potential duration (APD) and the effective refractory period (ERP) in cardiac myocytes mainly by blocking the IKr (the rapid component of delayed rectifier K+ current). The antiarrhythmic efficacy depends on prolongation of ERP. The importance of this drug is to save patients from the life-threatening arrhythmias ventricular tachycardia (VT) and fibrillation (VF). Nifekalant was effective against reentrant arrhythmias such as VT and VF in postinfarction dogs. This drug does not have the negative inotropic effect that has been observed with other antiarrhythmic drugs. In clinical therapy, this drug was remarkably effective on patients who were unresponsive to therapy with other drugs or who were not able to receive other drugs due to decreased cardiac function. There has been no case of drug-induced worsening of the cardiac function. The significant adverse reaction is proarrhythmia such as ventricular tachycardia including TdP. Nifekalant is expected to be a useful drug for patients who could not be rescued from life-threatening arrhythmia by conventional therapies.
Oyabe
Akihiro
A
Drug Discovery Institute, Nihon Schering K.K., 1900-1, Togo, Mobara, Chiba 297-0017, Japan.
Sano
Hidetoshi
H
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011744:Pyrimidinones / Q000494:pharmacology* / Q000627:therapeutic use*
D000889:Anti-Arrhythmia Agents; D011744:Pyrimidinones; C076259:nifekalant