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)

1991-02-01·Arzneimittel-Forschung

Antiarrhythmic effects of two new propafenone related drugs. A study on four animal models of arrhythmia.

Article

作者: Kukovetz, W R ; Wascher, T C ; Dittrich, P

LG 6-101 (1-[3-(2-methoxy-3-(2-methylpropylamino)-propoxy)-4-methyl- 2-thienyl]-3-phenyl-1-propanone, hydrochloride) and LG 6-102 (2-(2-methoxy-3-propylamino-propoxy)-3-phenyl-propiophenone, hydrochloride) are two new antiarrhythmic drugs. They are structurally related to propafenone which is a widely used class 1 antiarrhythmic drug with relatively low bioavailability. Both substances were characterized in four animal models of arrhythmia and compared to propafenone. In isolated guinea pigs left auricles LG 6-101 and LG6-102 were about twice as effective as propafenone regarding the prolongation of the functional refractory period but did not decrease contractility more than propafenone. LG 6-101 was significantly more effective (p less than or equal to 0.002) than propafenone or LG 6-102 in delaying the onset of ventricular premature beats in ouabain induced arrhythmias in guinea pigs. In aconitine induced arrhythmias in rats, LG 6-101 and LG 6-102 did not differ in their antiarrhythmic effects from propafenone, whereas the protection against cardiac arrest was significantly (p less than or equal to 0.003) better for LG 6-101 than for propafenone or LG 6-102. In arrhythmias induced by occlusion of the left descending coronary artery in rats the drugs tested showed as good antiarrhythmic effects as propafenone. In this model the size of the ischemic area was also measured and LG 6-101 was the most effective drug in that respect. These results suggest that both LG 6-101 and LG 6-102 are potent antiarrhythmic substances which in some models were more effective than propafenone.

100 项与 LG-6102 相关的药物交易

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