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  • Title: LG 6-101 and LG 6-102, two new propafenone-related antiarrhythmic agents with good oral activity in rats.
    Author: Wascher TC, Dittrich P, Kukovetz WR.
    Journal: Naunyn Schmiedebergs Arch Pharmacol; 1992 Apr; 345(4):473-7. PubMed ID: 1620247.
    Abstract:
    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)
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