digoxin and acrihellin

3 beta,5,14-Trihydroxy-19-oxo-5 beta-bufa-20,22-dienolide 3-(3-methylcrotonate) (acrihellin, D 12 316) is according to chemical structure and pharmacological effects a semisynthetic compound of the aglycon hellebrigenin. It is characterized as a cardiosteroid. In isolated organ (Langendorff heart) the positive inotropic effect proved to be stronger in comparison to digoxin. Also in dogs and cats acrihellin increases the contractile force of the myocardium; especially in failing canine heart, it increases the force of contraction (strain-gauge) and velocity of pressure rise (dp/dt max). In classical glycoside test on cat (Hatcher's dose) acrihellin is more effective than digoxin and methyldigoxin on weight basis, equivalent on a molar basis. The therapeutical index of acrihellin is like that of methyldigoxin. In cats and dogs, the compound is absorbed rapidly and almost completely, especially when administered intraduodenally. Herein it is comparable to methyldigoxin, better than digoxin. In cats acrihellin shows a decay rate of 26%. In all investigations performed in order to study central nervous effects after single administration of therapeutical doses no central side-effects could be detected in contrast to methyldigoxin.

Topics: Anesthesia; Animals; Anticonvulsants; Ataxia; Bufanolides; Cardiac Glycosides; Cats; Digoxin; Dogs; Female; Gastrointestinal Motility; Guinea Pigs; Hemodynamics; Hexobarbital; In Vitro Techniques; Male; Mice; Motor Activity; Myocardial Contraction; Rats; Reflex; Sleep; Stomach Ulcer

The inotropic effects of the new cardiotonic drug 3 beta,5,14-trihydroxy-19-oxo-5 beta-bufa-20,22-dienolide-3-(3-methylcrotonate) (D 12316, acrihellin) were investigated using twitch contractions time to peak and twitch lengths did not change. Peak tension increased by 140% on an average in 12 experiments at 10(-6) mol/l (acrihellin). In the dose-response curve half maximal positive inotropism occurred at approx. 10(-7) mol/l. Experiments on length tension relationships of resting and twitch tension confirmed that resting tension does not change at any stretch length after administering acrihellin. The position Lmax of maximal twitch contraction force also was not changed but in normalized length-tension cones the positive slope region showed an increase relative to maximal tension which is a feature of positive inotropic interventions. Measurements of contractility in various external calcium solutions between 0.45 mmol/l and 7.2 mmol/l gave evidence that the response of contraction force of fibres exposed to acrihellin to variation of external calcium differs from untreated fibres which respond more strongly. This behaviour of the cardiosteroid acrihellin was very similar to that of adrenaline (epinephrine) whereas digoxin and ouabain did not affect the response of twitch force to changes in external calcium.

Topics: Animals; Bufanolides; Calcium; Cardiotonic Agents; Digoxin; Drug Interactions; Electrophysiology; Epinephrine; In Vitro Techniques; Myocardial Contraction; Sheep