Digitalis-like Action Research Articles

Impact of 13(S)-HPODE, a lipoxygenase product of linoleic acid, on calcium transport and Na,K-ATPase activity in the myocardial sarcolemma

In thisin vitro study using a purified sarcolemmic fraction of guinea pig myocardium, the 13(S)-hydroperoxide of linoleic acid (13-HPODE) increased in a dose-dependent manner the permeability of myocardial sarcolemma to Ca ions in concentrations above 10 μmol/liter, stimulated Na/Ca exchange there in concentrations from 0.1 to 10 μmol/liter, and exerted a digitalis-like action on sarcolemmic Na,K-ATPase in concentrations between 0.1 and 100 μmol/liter (IC50=20 μmol/liter). The results indicate that the linoleic acid hydroperoxide may be an effective modulator of sarcolemmic Ca2+ transport and of membrane-bound enzymes.

Regulation of active cation flux by vanadate in beating rat heart muscle cells in culture.

Looking for a supposed digitalis-like action of compounds of the trace element vanadium, we have investigated the influence of vanadate (Na3VO4) on beating and on active cation flux of [42K+] and [89Rb+] in cultured rat heart muscle cells: Na3VO4(10(-6)-10(-3)M) exerts a positive chronotropic effect and increases contraction velocity and beating automaticity of the cells. Vanadate-induced alteration of beating is paralleled by stimulated uptake of [42K+] and [86Rb+] up to 75%. This stimulation has to be attributed to increased activity of (Na++)-ATPase and cannot solely be explained by the enhanced beating frequency. In contrast to ouabain, vanadate raises intracellular potassium content up to 15% and prevents cell contractures of ouabain-intoxicated heart muscle cells. The experimental data speak against a possible digitalis-like action of vanadate in cultured rat heart muscle cells.

Die indirekt sympathicomimetische Wirkung von Heptaminol auf den Herzmuskel

On the isolated guinea-pig papillary muscle heptaminol causes half maximal inotropic effect in a concentration of 4×10−4 M. A variation of the extracellular potassium concentration between 2.4 and 9.6 mM as well as a reduction of the extracellular sodium concentration from 140 mM to 70 mM have no influence on the action of heptaminol; this would have been characteristic for a digitalis-like action. The positive inotropic effect is suppressed by 5×10−4 M propranolol and by pretreatment of the animal with 5 mg/kg reserpine. The action of heptaminol, therefore, is clearly that of an indirectly acting sympathomimetic amine.

A new glycoside of [formula omitted

Abstract A new glycoside, Substance N, has been isolated from the leaves of Adonis vernalis by fractional paper chromatography. It has a highly potent digitalis-like action, the geometrical mean LD being 0.1141 ± 0.0040 mg/kg in cats.

Activities of newer glycosides of [formula omitted

Abstract The digitalis-like action of 5 substances, naturally occuring or partially synthetized from the aglycones of Adonis vernalis L. has been verified. Their activity as measured by LD in etherized cats has been determined.

MECHANISM OF CARDIOVASCULAR ACTIONS OF HEPTANOLAMINES

It has been suggested that heptaminol and methylheptaminol should be used as myocardial stimulants because they have cardiotonic actions similar to those of cardiac glycosides. However, as these aliphatic amines show definite sympathomimetic effects, the mechanism of their actions on the heart was investigated, in order to determine whether digitalis-like properties are involved in these effects. The pattern of pharmacological actions of heptaminol and methylheptaminol was compared with that of catechol amines, tyramine and k-strophanthin. The influence of atropine, hexamethonium, cocaine and reserpine was also investigated. The results show that both heptanolamines have a long-lasting cardiostimulant action which is abolished by cocaine and absent in reserpine pretreated animals. The pharmacological activity of these drugs may be entirely attributed to an indirect sympathomimetic action of the tyramine type, probably due to release of endogenous catechol amines. None of the experimental findings is consistent with the alleged digitalis-like action of these compounds.

Comparison of cardiac action of bufalin, cinobufotalin, and telocinobufagin with cinobufagin.

SummaryThe cardiac activity of bufalin, cinobufotalin, telocinobufagin and cinobufagin has been compared. They all have a digitalis-like action. In etherized cats the order of activity from high to low is telecinobufagin > bufalin > cinobufotalin = cinobufagin.

Digitalis-like action of some new glycosides and esters of strophanthidin: Chen, K. K., and Anderson, R. C.: J. Pharmacol. & Exper. Therap. 90:271 (July), 1947

Digitalis-like action of some new glycosides and esters of strophanthidin: Chen, K. K., and Anderson, R. C.: J. Pharmacol. & Exper. Therap. 90:271 (July), 1947

CLINICAL OBSERVATIONS IN TYPHUS FEVER

This study was undertaken principally to observe the various physiologic changes occurring in typhus fever with special attention directed to the status of the general circulation. Previous descriptions of the disease frequently refer to cardiac collapse, cardiac or cardiac weakness and in areas where typhus is prevalent it is almost a routine procedure to administer cardiac stimulants in the form of digitalis, ouabain or perhaps some other substitute. Likewise, in certain sections cardiac drugs are given because of the extremely weak and toxic appearance of the patient with the thought in mind that these cardiac tonics will improve the circulation. The latter is not in accord with the actual physiologic effect of digitalis, and Luten 1 has shown that the only clinical indication for digitalis and drugs with digitalis-like action is evidence of cardiac failure and in certain arrhythmias. In our study there was no clear indication for cardiac

Synthetic derivatives of strophanthidin: Chen, K. K., and Elderfield, R. C.: J. Pharmacol. & Exper. Therap. 76: 81, 1942

1. Strophanthidin acetate and 7 synthetic glycosides of strophanthidin all have a digitalis-like action. 2. When assayed in cats and frogs, strophanthidin acetate, strophanthidin-β- d -glucoside, - d -xyloside, and - l -arabinoside, prove more potent than strophanthidin. Strophanthidin-β-tetraacetyl- d -glucoside, -triacetyl- d -xyloside, -triacetyl- l -arabinoside, and -tetraacetyl- d -galactoside, on the other hand, are weaker than strophanthidin. 3. Strophanthidin-β- d -glucoside and - l -arabinoside are also more potent than cymarin, the natural glycoside from which strophanthidin is originally obtained. Strophanthidin-β- d -xyloside is at least as active as cymarin.

The action of simple lactones related to cardiac aglycones: Chen, K. K., Steldt, F. A., Fried, J., and Elderfield, R. C.: J. Pharmacol. & Exper. Therap. 74: 381, 1942

1. Twenty-seven unsaturated lactones related to cardiac aglycones have been studied pharmacologically. 2. β,γ-Angelica lactone, the lactone of 21 -hydroxy-Δ20,22-norcholenic acid, methyl coumalate, and ethyl coumalate, cause systolic standstill of frogs' ventricles when adequate doses are injected into the ventral lymph sac. β-(β-Naphthyl)-Δα,β-butenolide has a suggestive action. 3. In cats, β,υ-angelica lactone and methyl and ethyl coumalates all produce a fall of blood pressure and fail to induce emesis. Electrocardiographically, no ectopic rhythm, multiple foci of impulse formation, various forms of aberrant QRS complexes, and terminal ventricular fibrillation occur as the lethal dose is slowly approached. The evidence in cats is therefore not indicative of any digitalis-like action of the three substances.

Effect on the Electrocardiogram of Coumingine Hydrochloride, a New Alkaloid with Digitalis-like Action

Conclusions1. The parenteral administration of coumingine hydrochloride, a new alkaloid, produced electrocardiographic disturbances in dogs and cats similar to those of digitalis. 2. The cat unit by the Hatcher and Brody method was found to be 0.159 mg per kg, confirming the result of Chen. 3. Daily intramuscular injections in dogs of variable sublethal doses of coumingine hydrochloride revealed that the onset of electrocardiographic disturbances was slower than after comparable doses of digitalis. The rate of disappearance of P.R prolongation after injections were discontinued, was essentially the same. However, the myocardial irritation of coumingine hydrochloride indicated by T-wave changes, was less persistent than after digitalis administration. 4. Toxic symptoms were essentially similar to those noted in digitalized controls but were milder in character. 5. Local inflammatory reaction following intramuscular injection of moderate or large doses of coumingine hydrochloride was marked.