Structure-activity relationships of an aminosugar cardiac glycoside, ASI-222 HCl, in the heart-lung preparation of the dog

L. Scott Cook, Robert William Caldwell, Clinton B. Nash

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

ASI-222 [3-β-O-(4-amino-4, 6-dideoxy-β-D-galactopyranosyl) digitoxigenin HCl] is a semisynthetic aminosugar cardiac glycoside that has been shown to have a greater therapeutic index than ouabain or digoxin in dogs. We have compared the effects of ASI, digitoxigenin, digitoxigenin-β-D-galactose, and digoxin in the dog heart-lung preparation. Minute work and stroke work were calculated. Controls were obtained before and after the hearts were failed with sodium pentobarbital. ASI-222 is about three times more potent than digitoxigenin and about twice as potent as digitoxigenin-β-D-galactose in producing similar increases in the left ventricular stroke work. ASI-222 is about three times more potent than digoxin in increasing left ventricular stroke work. Our results indicate that the addition of an aminosugar group to the genin further increased potency over that observed with the addition of a single neutral sugar and prolonged the duration of activity in failing myocardial tissue.

Original languageEnglish (US)
Pages (from-to)551-559
Number of pages9
JournalJournal of Cardiovascular Pharmacology
Volume1
Issue number5
StatePublished - Jan 1 1979
Externally publishedYes

Fingerprint

Digitoxigenin
Cardiac Glycosides
Digoxin
Structure-Activity Relationship
Stroke
Dogs
Galactose
Lung
Ouabain
Pentobarbital
ASI-222
digitoxigenin-galactose
Therapeutics

Keywords

  • Aminosugar cardiac glycosides
  • ASI-222
  • Cardiac glycosides

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Structure-activity relationships of an aminosugar cardiac glycoside, ASI-222 HCl, in the heart-lung preparation of the dog. / Scott Cook, L.; Caldwell, Robert William; Nash, Clinton B.

In: Journal of Cardiovascular Pharmacology, Vol. 1, No. 5, 01.01.1979, p. 551-559.

Research output: Contribution to journalArticle

@article{9a9ef44acb1f41b28dfc224753e31a6e,
title = "Structure-activity relationships of an aminosugar cardiac glycoside, ASI-222 HCl, in the heart-lung preparation of the dog",
abstract = "ASI-222 [3-β-O-(4-amino-4, 6-dideoxy-β-D-galactopyranosyl) digitoxigenin HCl] is a semisynthetic aminosugar cardiac glycoside that has been shown to have a greater therapeutic index than ouabain or digoxin in dogs. We have compared the effects of ASI, digitoxigenin, digitoxigenin-β-D-galactose, and digoxin in the dog heart-lung preparation. Minute work and stroke work were calculated. Controls were obtained before and after the hearts were failed with sodium pentobarbital. ASI-222 is about three times more potent than digitoxigenin and about twice as potent as digitoxigenin-β-D-galactose in producing similar increases in the left ventricular stroke work. ASI-222 is about three times more potent than digoxin in increasing left ventricular stroke work. Our results indicate that the addition of an aminosugar group to the genin further increased potency over that observed with the addition of a single neutral sugar and prolonged the duration of activity in failing myocardial tissue.",
keywords = "Aminosugar cardiac glycosides, ASI-222, Cardiac glycosides",
author = "{Scott Cook}, L. and Caldwell, {Robert William} and Nash, {Clinton B.}",
year = "1979",
month = "1",
day = "1",
language = "English (US)",
volume = "1",
pages = "551--559",
journal = "Journal of Cardiovascular Pharmacology",
issn = "0160-2446",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Structure-activity relationships of an aminosugar cardiac glycoside, ASI-222 HCl, in the heart-lung preparation of the dog

AU - Scott Cook, L.

AU - Caldwell, Robert William

AU - Nash, Clinton B.

PY - 1979/1/1

Y1 - 1979/1/1

N2 - ASI-222 [3-β-O-(4-amino-4, 6-dideoxy-β-D-galactopyranosyl) digitoxigenin HCl] is a semisynthetic aminosugar cardiac glycoside that has been shown to have a greater therapeutic index than ouabain or digoxin in dogs. We have compared the effects of ASI, digitoxigenin, digitoxigenin-β-D-galactose, and digoxin in the dog heart-lung preparation. Minute work and stroke work were calculated. Controls were obtained before and after the hearts were failed with sodium pentobarbital. ASI-222 is about three times more potent than digitoxigenin and about twice as potent as digitoxigenin-β-D-galactose in producing similar increases in the left ventricular stroke work. ASI-222 is about three times more potent than digoxin in increasing left ventricular stroke work. Our results indicate that the addition of an aminosugar group to the genin further increased potency over that observed with the addition of a single neutral sugar and prolonged the duration of activity in failing myocardial tissue.

AB - ASI-222 [3-β-O-(4-amino-4, 6-dideoxy-β-D-galactopyranosyl) digitoxigenin HCl] is a semisynthetic aminosugar cardiac glycoside that has been shown to have a greater therapeutic index than ouabain or digoxin in dogs. We have compared the effects of ASI, digitoxigenin, digitoxigenin-β-D-galactose, and digoxin in the dog heart-lung preparation. Minute work and stroke work were calculated. Controls were obtained before and after the hearts were failed with sodium pentobarbital. ASI-222 is about three times more potent than digitoxigenin and about twice as potent as digitoxigenin-β-D-galactose in producing similar increases in the left ventricular stroke work. ASI-222 is about three times more potent than digoxin in increasing left ventricular stroke work. Our results indicate that the addition of an aminosugar group to the genin further increased potency over that observed with the addition of a single neutral sugar and prolonged the duration of activity in failing myocardial tissue.

KW - Aminosugar cardiac glycosides

KW - ASI-222

KW - Cardiac glycosides

UR - http://www.scopus.com/inward/record.url?scp=0018569359&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0018569359&partnerID=8YFLogxK

M3 - Article

VL - 1

SP - 551

EP - 559

JO - Journal of Cardiovascular Pharmacology

JF - Journal of Cardiovascular Pharmacology

SN - 0160-2446

IS - 5

ER -