A Third Class of Anti-arrhythmic Action. Effects on Atrial and Ventricular Intracellular Potentials, and Other Pharmacological Actions on Cardiac Muscle, of MJ 1999 and AH 3474

1. Both MJ 1999 and AH 3474 protected guinea-pigs anaesthetized with urethane against ouabain-induced ventricular fibrillation.2. MJ 1999 had 1/90, and AH 3474 1/30, of the activity of procaine in reducing the height of the action potential of frog sciatic nerve.3. MJ 1999 and AH 3474 reduced the rate of rise of intracellularly recorded action potentials at concentrations in excess of 160 x 10(-6)M (50 mg/l.). It was concluded that direct depression of depolarization could have contributed little to the protection against ouabain-induced fibrillation.4. MJ 1999, but not AH 3474, greatly prolonged the duration of the action potential in acute experiments on isolated atrial and ventricular muscle, and prolonged the Q-Tc interval of the electrocardiogram in anaesthetized guinea-pigs. It is suggested that this effect contributes to anti-arrhythmic activity.5. At concentrations up to 80 x 10(-6)M AH 3474 had positive chronotropic and inotropic effects on isolated rabbit atrial muscle, but at higher concentrations these were superseded by negative effects. MJ 1999 was depressant at all concentrations studied, the threshold concentrations being 19 x 10(-6)M for chronotropic, and 162 x 10(-6)M for inotropic effects.