Detail of "74517-78-5"

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Electrophysiological studies of indecainide hydrochloride, a new antiarrhythmic agent, in canine cardiac tissues

Electrophysiological studies of indecainide hydrochloride, a new antiarrhythmic agent, in canine cardiac tissues. Steinberg, Mitchell I.; Wiest, Sally A. (Dep. Cardiovasc. Pharmacol., Lilly Res. Lab., Indianapolis, IN, USA). J. Cardiovasc. Pharmacol., 6(4), 614-21 (English) 1984. CODEN: JCPCDT. ISSN: 0160-2446. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The intracellular electrophysiol. properties of indecainide (I) [74517-78-5] were studied in isolated canine myocardial prepns. stimulated at 1 Hz and superfused with Tyrode's soln. In Purkinje fibers, indecainide (10-6 and 3 ′ 10-6M) decreased the maximal rate of rise of phase 0 (Vmax), conduction velocity, action potential duration (ADP), and effective refractory period, and shifted the membrane-response curve by 5 mV in a hyperpolarizing direction. In papillary muscle, APD was unchanged, but Vmax was decreased. The effect of the drug on Vmax was rate-dependent, but over physiol. relevant cycle lengths (370-1000 ms), Vmax remained relatively const. In the presence of indecainide (3 ′ 10-6M) and at a basic cycle length of 333 ms, the rate-consts. for block onset were 0.06 and 0.1 action potentials-1 in Purkinje fiber and papillary muscle, resp. The recovery of Vmax from max. steady-state block was half completed in Purkinje fibers and muscle in 52 and 49 s, resp. No resting block was apparent in either tissue at normal resting membrane potential. Indecainide had only minimal effects on automaticity arising from normal or depolarized (Ba) membrane potentials. Thus, indecainide is a potent class-I local-anesthetic antiarrhythmic agent that depresses Vmax and conduction in cardiac tissues. The depressant effects of indecainide are completely dependent on prior activation of the tissue, but because of its slow kinetics for recovery from Na+-channel block, little addnl. change in Vmax occurs within physiol. relevant heart rates and prematurity intervals.

Liquid chromatographic determination of indecainide, a new antiarrhythmic drug, and its major metabolite, desisopropylindecainide, in biological samples

Liquid chromatographic determination of indecainide, a new antiarrhythmic drug, and its major metabolite, desisopropylindecainide, in biological samples. Farid, Khadiga Z.; Fasola, Alfred F.; Nash, J. Frank (Lilly Res. Lab., Eli Lilly Co., Indianapolis, IN 46285, USA). J. Chromatogr., 337(2), 329-40 (English) 1985. CODEN: JOCRAM. ISSN: 0021-9673. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) A simple, sensitive, and selective method for the detn. of indecainide (I) [74517-78-5] and its metabolite, deisopropylindecainide [79156-86-8] in human plasma (or serum) and urine is described. The compds. are extd. from alkalinized plasma or urine samples with EtOAc-hexane (9:1), the solvent is evapd. under N and the residue is reconstituted in the mobile phase. The compds. are chromatographed on a Zorbax C8 column, using 0.25 M ammonium acetate-MeCN-MeOH-tetrahydrofuran (:) as the eluent at 1.5 mL/min. The effluent is monitored at 270 nm or by using a fluorescence detector (lexc 270 nm, lem 315 nm).