Method for the treatment of cardiac arrhythmias and shortening o

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...

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A61K 3116

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058407626

ABSTRACT:
The invention relates to the use of zucapsaicin (cis-8-methly-N-vanillly-6-nonenamide), the cis-isomer of capsaicin, to treat myocardial disorders, including the prevention, suppression or reversal of an abnormal cardiac rhythm, such as ventricular tachycardia. In vitro, zucapsaicin exhibits electrophysiologic properties distinct from capsaicin. In contrast to capsaicin, zucapsaicin significantly shortens the action potential duration at a dose of 10.sup.-5 M and has no effect on the amplitude of Phase 1 of the action potential in normal Purkinje cells. Zucapsaicin also prevents the induction of ventricular tachycardia of focal Purkinje origin when given intravenously after coronary occlusion in a dog model of acute myocardial infarction.

REFERENCES:
patent: 5063060 (1991-11-01), Bernstein
Samson, et al., 1995. Electrophysiological effects of .alpha..sub.2 -adrenergic stimulation in canine cardiac Purkinje fibers, Am. J. Physiol. 268: H2024-H2035.
Martins, J., 1995. Purkinje involvement at focal origin of ischemic ventricular tachycardia. J. Invest. Med. 43: 431A (Abstract).
Castle, Neil A., 1992. Differential inhibition of potassium currents in rat ventricular myocytes by capsaicin. Cardiovasc. Res. 26: 1137-1144.
D'Alonzo, A.J., et al., 1995. In vitro effects of capsaicin: antiarrhythmic and antiischemic activity. Eur. J. Pharmacology 272: 269-278.
Franco-Cereceda, A., et al., 1988. Calcitonin gene-related peptide: release by capsaicin and prolongation of the action potential in the guinea-pig heart. Acta. Physiol. Scand. 132: 181-190.
Nakajima, T., et al., 1991. Effects of calcitonin gene-related peptide on membrane currents in mammalian cardiac myocytes. Eur. J. Physiology 419: 644-650.
Hess, T.A., et al., 1994. In vitro antiarrhythmic and antiischemic effects of capsaicin, a K.sup.+ channel modulator. FASEB Abstracts (II) 3530.
Physician' Desk Reference, vol. 50, 1996. Dolorac.TM., p. 1054; Zostrix.RTM. and Zostrix.RTM.-HP, p. 1056.

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