Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1996-10-29
1998-03-31
Henley, III, Raymond
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
A61K 3170
Patent
active
057338892
ABSTRACT:
The present invention provides a novel treatment for cardiac arrhythmias, by administering S-adenosyl methionine decarboxylase inhibitors, preferably 5'-({(Z)-4-amino-2-butenyl}methylamino)-5'-deoxyadenosine. It has been discovered that 5'-({(Z)-4-amino-2-butenyl}methylamino)-5'-deoxyadenosine, increases the P--R interval, increases outward current through inward rectifier K.sup.+ channels and increases the hyperpolarization, of cardiac cells, thereby reducing cardiac excitability. Specifically, the method involves providing an S-adenosyl methionine decarboxylase inhibitor; combining the S-adenosyl methionine decarboxylase inhibitor with a pharmaceutically acceptable carrier to provide a pharmaceutical composition; administering an effective amount of the pharmaceutical composition to a patient suffering from a cardiac arrhythmia, wether such arrhythmias are induced by disease or cardiotoxicity. As a result of the treatment with S-adenosyl methionine decarboxylase inhibitor, spermine and spermidine levels are lowered in cardiac cells, the P--R interval is prolonged, cardiac excitability is reduced and the incidence of ventricular fibrillation, particularly sustained ventricular fibrillation is diminished. The method of the present invention is useful to terminate, prevent or reduce the incidence of cardiac arrhythmias, including, for example, ventricular tachycardia, atrial fibrillation ventricular fibrillation, particularly sustained ventricular fibrillation, and premature ventricular contractions.
REFERENCES:
patent: 4560795 (1985-12-01), Bey et al.
patent: 5416076 (1995-05-01), Casara et al.
"Regulation by Spermine of Native Inward Rectifier K+ Channels in RBL-1 Cells" by Bianchi, et al., J. Biol. Chem. 271(11), pp. 6114-6121, Mar. 1996.
"Effects of the S-adenosylmethione decarboxylase inhibitor . . . " by Byers, et al., Biochem J. 303(1), pp. 89-96, 1994.
"Polyamine-mediated regulation of S-adenosylmethione decarobxylase . . . " by Stjernborg, et al., Eur. J. Biochem. 214, pp. 671-676 (1993). Byers, et al., Biochem. J., 290(1), pp. 115-121, 1993.
"Inhibition of S-adenosyl-L-methionine (Adomet) Decarboxylase . . . " by Yakubu, et al., J. Parasitol, 79(4) pp. 525-532, 1993.
Henley III Raymond
The MetroHealth System
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