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Cardiostimulatory effects of oxyfedrine, DMPP and sympathomimetics in relation to their3H-noradrenaline-releasing properties

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Summary

The effect of noradrenaline, norephedrine, oxyfedrine and DMPP on isotonic contractions and release of3H-noradrenaline was studied using isolated perfused guinea-pig hearts.

The spontaneous rate of3H-release was linear from 30–70 min after infusion of a tracer dose of 20 ΜCi noradrenaline. The calculated size of the labeled noradrenaline-pool of the heart was 5–10% of the total noradrenaline-content.

Oxyfedrine (10 Μg) caused strong and long lasting positive inotropic effects but only a weak and transient increase of3H-release. Equimolar doses of 5Μg 1-norephedrine which is a component of the oxyfedrine molecule had no significant inotropic effect but caused similar increases in3H-release.

Noradrenaline (0.5 Μg, a dose with maximum positive inotropic action) released more3H-activity from the heart than oxyfedrine.

DMPP, a ganglion stimulating agent, in doses of 250 Μg, increased contractions significantly but had very little effect on3H-noradrenaline-release. An additional release of non-labeled noradrenaline is discussed as explanation of the positive inotropic action of DMPP.

After repeated administration of DMPP in large doses, the increase in contraction and3H-release was abolished. In this state of tachyphylaxis oxyfedrine also failed to release3H-noradrenaline but retained its full inotropic effect.

The results do not provide evidence that a releasing effect on labeled and/or non-labeled endogenous noradrenaline significantly contributes to the positive inotropic action of oxyfedrine. This finding supports the view that oxyfedrine stimulates the heart by adirect action on sympatheticΒ-receptors.

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  1. Department of Pharmacology, University of Graz, Austria

    W. R. Kukovetz & G. Pöch

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  1. W. R. Kukovetz
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  2. G. Pöch
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Kukovetz, W.R., Pöch, G. Cardiostimulatory effects of oxyfedrine, DMPP and sympathomimetics in relation to their3H-noradrenaline-releasing properties. Naunyn-Schmiedebergs Arch. Pharmak. 268, 59–70 (1971). https://doi.org/10.1007/BF00997173

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  • DOI: https://doi.org/10.1007/BF00997173

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