Nifekalant hydrochloride

Nifekalant is a novel and pure class III anti-arrhythmic agent introduced in Japan as Shinbit injection for the treatment of serious ventricular arrhythmias. It can be synthesized in 3 steps with a final assembly of two ethanolamine blocks. Nifekalant is a non-selective blocker of myocardial repolarizing potassium currents and is completely devoid of any β-adrenergic blocking effect . In hearts from different species, Nifekalant significantly prolonged action potential duration, atrial and ventricular refractory periods in in situ and in isolation studies. In intact animals, hemodynamic parameters were not affected by doses up to 1 mg/kg. The specific characteristics of its voltage- and timedependent K+ current blockade might differentiate Nifekalant from other class III agents currently in use.

Nifekalant is a class III antiarrhythmic agent that has been shown to be beneficial to initial resuscitation after cardiac arrest in clinical trials. It blocks the rapidly activating delayed rectifier potassium channel (I_Kr; IC₅₀ = 10 μM). Nifekalant is also inhibits the human multidrug and toxin extrusion (MATE) transporter 1 (MATE1; IC₅₀ = 6.5 μM).

Yellow Solid

Mitsui (Japan)

Nifekalant Hydrochloride is a class III antiarrhythmic agent. Nifekalant Hydrochloride is used in the treatment of patients with extensive anterior infarction and severe ventricular dysfunction.

ChEBI: Nifekalant hydrochloride is an amine. It contains a Nifekalant.

Shinbit

[1] TSUTOMU KATAKAMI. Synthesis and pharmacological studies of N-substituted 6-[(2-aminoethyl)amino]-1,3-dimethyl-2,4(1H,3H)-pyrimidinediones, novel class III antiarrhythmic agents[J]. Journal of Medicinal Chemistry, 1992, 35 18: 3325-3330. DOI: 10.1021/jm00096a003
[2] J KAMIYA  T K  M Ishii. Antiarrhythmic effects of MS-551, a new class III antiarrhythmic agent, on canine models of ventricular arrhythmia.[J]. Japanese journal of pharmacology, 1992, 58 2: 107-115. DOI: 10.1254/jjp.58.107
[3] JOJI KAMIYA. MS-551: Pharmacological profile of a novel class III antiarrhythmic agent[J]. Drug Development Research, 1993, 30 1: 37-44. DOI: 10.1002/ddr.430300106
[4] MATTHIAS B. WITTWER. Discovery of Potent, Selective Multidrug and Toxin Extrusion Transporter 1 (MATE1, SLC47A1) Inhibitors Through Prescription Drug Profiling and Computational Modeling[J]. Journal of Medicinal Chemistry, 2012, 56 3: 781-795. DOI: 10.1021/jm301302s