LG 6-101 (1-[3-(2-methoxy-3-(2-methylpropylamino)-propoxy)-4-methyl- 2-thienyl]-3-phenyl-1-propanon hydrochloride; MW: 426.02) and
LG 6-102 (2-(2-methoxy-3-propylamino-propoxy)-3-phenyl-propiophenon hydrochloride; MW: 391.92) are two new antiarrhythmic substances. They are structurally related to
propafenone which is a widely used class Ic-
antiarrhythmic drug. In man the oral bioavailability of
propafenone is only about 5-40%. Therefore the development of compounds with similar mode of action but higher oral bioavailability seems to be meaningful. Both,
LG 6-101 and
LG 6-102 proved to be effective in isolated auricles and in experimental animals after
intravenous administration. In the present study we tested the antiarrhythmic effects of
LG 6-101 and
LG 6-102 in rats after
oral administration. Animals were treated with
LG 6-101 (16, 32, 64, 128, 256 mg kg-1 bodyweight),
LG 6-102 (4, 8, 16, 32, 64 mg kg-1 bodyweight) and
propafenone (32, 64, 128, 256 mg kg-1 bodyweight) by gavage twice daily during 4 days. Both,
LG 6-101 and
LG 6-102 showed strong antiarrhythmic effects against arrhythmias induced on the fifth day by infusion of
aconitine (10 micrograms kg-1 min-1).
LG 6-102 was significantly more effective against
cardiac arrest caused by infusion of
aconitine (P less than or equal to 0.05) than
LG 6-101. Both substances had good effects on the delay of ventricular
premature beats.(ABSTRACT TRUNCATED AT 250 WORDS)