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. 1970 Nov;40(3):373–381. doi: 10.1111/j.1476-5381.1970.tb10619.x

Comparative chronotropic activity of β-adrenoceptive antagonists

A M Barrett, J Carter
PMCID: PMC1703170  PMID: 4395742

Abstract

1. Chronotropic dose-response curves (non-cumulative) for β-adrenoceptive antagonists were constructed from results in rats anaesthetized with pentobarbitone and depleted of catecholamines by pre-treatment with syrosingopine.

2. Depletion of catecholamines lowered resting heart rate and reduced the threshold to the chronotropic action of isoprenaline by about 50%. Eight β-adrenoceptive antagonists produced a dose-dependent chronotropic response but the maximum response was in all cases smaller than that obtained with isoprenaline. The order of activity was dichloroisoprenaline>LB 46>practolol>INPEA>oxprenolol>pronethalol>alprenolol>I.C.I. 45,763 (Kö 592). Propranolol and sotalol were without significant activity. The duration of the chronotropic response to the antagonists was more prolonged than that to isoprenaline. Propranolol caused a parallel shift to the right of the dose-response curves for the agonist effects of the antagonists.

3. Estimation of β-adrenoceptor blocking activity in anaesthetized cats gave an order of activity dissimilar to that found for maximum agonist responses: LB 46 > oxprenolol > alprenolol > propranolol > I.C.I. 45,763 > practolol > dichloroisoprenaline > sotalol > INPEA > pronethalol.

4. Consideration of chemical structure and physico-chemical properties did not explain the differences between the agonist activities of the adrenoceptive antagonists.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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