The effects of digitoxin and its metabolites on the transmembrane potential and contractile characteristics of guinea-pig ventricle strips.
The effects of 10(-7) and 10(-6) M digitoxin, and some of its metabolites, digitoxigenin-bis-digitoxoside, digitoxigenin-mono-digitoxoside and digitoxigenin on the transmembrane potential and contractile characteristics of guinea-pig right ventricle strips were studied to define the role of the sugar side-chain in these cleavage products of digitoxin. Digitoxin and digitoxigenin produced their maximum inotropic responses, without induction of arrhythmias, at about 30 min. However, the bis and mono compounds produced arrhythmias within 12 min, so the inotropy recorded may not be the maximum response. Digitoxin with 3 sugar residues and the bis compound with 2 sugar residues produced a prolongation in the action potenital duration. In contrast, the mono compound with one sugar residue and the digitoxigenin with no sugar residue produced a shortening of the action potential duration. There may be a relationship between the number of sugar moieties and the action potential duration; digitoxin and its bis derivative increased the action potential duration and mono- and digitoxigenin decreased the action potential duration. There also appeared to be an unusual relationship between the number of sugar moieties and induction of arrhythmias; arrhythmogenicity occurred at the doses employed with only the bis- and mono-digitoxoside. Finally, there appeared to be no simple relationship between chemical structure and inotropic potency.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004073:Digitoxigenin / Q000494:pharmacology; D004074:Digitoxin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013997:Time Factors
D004073:Digitoxigenin; D004074:Digitoxin