ISSN:
1432-1912
Keywords:
Strophanthidin-3-bromoacetate (SBA)
;
Papillary Muscle
;
Inotropic Effects
;
Time Course
;
Strophanthidin-3-bromacetat
;
Papillarmuskel
;
inotrope Wirkung
;
Zeitverlauf
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary In experiments on isolated, electrically stimulated papillary muscles or auricles of guinea pig hearts some characteristics of the inotropic action of strophanthidin-3-bromaocetate (SBA), a derivative of k-strophanthidin which is supposed to be an irreversible inhibitor of the (Na+-K+)-activated ATPase, were studied and compared with the behaviour of k-strophanthidin and digitoxin. The dose-response curves were shifted to higher concentrations in the following order: digitoxin 〈 k-strophanthidin 〈 SBA, (ED50: 3.2×10−7M; 3.5×10−6M; 9.1×10−6M), but with each of these substances the same maximum effect could be obtained. To test the reversibility of the observed pharmacological effects the time course of the changes in contractility was followed in washout experiments. Digitoxin showed the slowest rate of decline (t 1/2≈30 min), k-strophanthidin the most rapid (t 1/2≈3.5 min), and SBA had an intermediate position due to a biphasic washout curve which showed that 70% of the inotropic effect was eliminated with a halftime of about 2 min (similar to k-strophanthidin) and 30% with a halftime of about 20 min (similar to digitoxin). A similar behaviour was observed in the rate of development of the positive inotropic effects. The halftime of this process was around 1 min with k-strophanthidin, and 5 min with digitoxin, whereas the effect of SBA showed again a biphasic time course: 30% of the positive inotropic effect developed with a t1/2 of about 3 min and 70% with at1/2 of about 20 min. Due to the reversibility of the pharmacological action of SBA it has been concluded that (a) either the inotropic action of this substance is not mediated by an inhibition of the (Na+-K+)-activated ATPase or (b) that this enzyme is not inhibited irreversibly by SBA under the prevailing conditions. The biphasic time course of the SBA action is discussed tentatively on the assumption of two specific receptors with different affinities for this drug.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01020074
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