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  • Title: Investigations into the bradycardic effects of UL-FS 49 (1,3,4,5-tetrahydro-7,8-dimethoxy-3-[3-[[2-(3,4-dimethoxyphenyl)ethyl] methylimino]propyl]-2H-3-benzazepin-2-on-hydrochloride) in isolated guinea pig atria.
    Author: Lillie C, Kobinger W.
    Journal: J Cardiovasc Pharmacol; 1986; 8(4):791-7. PubMed ID: 2427820.
    Abstract:
    The new bradycardic agent UL-FS 49 (1,3,4,5-tetrahydro-7,8-dimethoxy-3-[3-[[2-(3,4-dimethoxyphenyl]ethyl] methylimino]propyl]-2H-3-benzazepin-2-on-hydrochloride) was investigated in isolated guinea pig atria. In spontaneously beating preparations UL-FS 49, (0.03 and 0.1 microgram/ml) reduced the rate of contraction and decreased the maximal effect of isoprenaline added thereafter. The cumulative concentration-response curve of isoprenaline was antagonized, but not in a competitive manner, excluding an interaction at the beta-adrenoceptor. The rate of spontaneous electrical activity in sinoatrial node preparations was increased by superfusion with isoprenaline (0.1 microgram/ml). Addition of UL-FS 49 (0.1 microgram/ml) as well as propranolol (0.3 microgram/ml) reduced rate to control values. In electrically driven (1 Hz) left atria UL-FS 49 (1 microgram/ml) did not reduce contractile force and did not antagonize the positive inotropic effect of isoprenaline added cumulatively thereafter. When contractile force was first elevated by isoprenaline (0.1 microgram/ml), addition of UL-FS 49 (0.1 microgram/ml) did not affect contractility, whereas propranolol (0.3 microgram/ml) abolished the positive inotropic effect of isoprenaline. The experiments, therefore, demonstrate the specificity of UL-FS 49 to decrease heart rate but not contractility during beta-adrenoceptor stimulation. In contrast to propranolol (0.3 microgram/ml) UL-FS 49 (0.1 microgram/ml) also reduced sinoatrial rate elevated by histamine (1 microgram/ml) or theophylline (300 micrograms/ml), thus indicating a possible use as an antitachycardic drug at tachycardias of various origins. In sinus node preparations depolarized by high external K+ concentrations (10.8 mM), the bradycardic effect of UL-FS 49 (0.1 microgram/ml) was diminished.(ABSTRACT TRUNCATED AT 250 WORDS)
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