Cell lines

HEK293 cells, guinea pig cardiomyocytes

Preparation method

The solubility of this compound in DMSO is >21.2 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

1 μM

Applications

In a human cell line and human embryonic kidney 293 transfected with HERG, dofetilide induced channel block with the EC50 of 12 ± 2 nM. Induction of block depended on depolarization beyond the threshold for channel opening. Dofetilide acted as a slow-onset/slow-offset open channel blocker of this current at nanomolar concentrations. Dofetilide (1 μM) reduced the amplitude of IKr to 61% of control currents in guinea pig cardiomyocytes, as measured by 200-ms test pulses and analysis of the deactivating tail currents of IKr.

Animal models

Dogs with old myocardial infarction (MI)

Dosage form

Intravenous injection, 100 mg/kg

Application

Dofetilide (100 mg/kg, i.v.) suppressed the reentry arrhythmia induced by PES in dogs with old myocardial infarction (MI). Dofetilide showed antiarrhythmic effect in some dogs with digitalis arrhythmia. Dofetilide increased QT interval and showed negative chronotropic effect.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Dofetilide(Tikosyn) is a class III antiarrhythmic agent.Target: Potassium ChannelIn patients with congestive heart failure and reduced left ventricular function, dofetilide was effective in converting atrial fibrillation, preventing its recurrence, and reducing the risk of hospitalization for worsening heart failure. Dofetilide had no effect on mortality [1]. dofetilide preferentially blocks open (or activated) channels and that the fast inactivation may competitively slow the binding kinetics. Dofetilide acts as a slow-onset/slow-offset open channel blocker of this current at nanomolar concentrations [2].

References:
[1]. Maisch, B., et al., [Pregnancy and cardiomyopathies]. Herz, 2003. 28(3): p. 196-208.
[2]. Snyders, D.J. and A. Chaudhary, High affinity open channel block by dofetilide of HERG expressed in a human cell line. Mol Pharmacol, 1996. 49(6): p. 949-55.