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Year : 1992  |  Volume : 24  |  Issue : 1  |  Page : 18-24

Are all beta-adrenoceptor blockers really competitive antagonists to beta-adrenoceptors?

Correspondence Address:
S D Mistry

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Source of Support: None, Conflict of Interest: None

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If two beta adrenoceptor antagonists are to act together, the theory predicts that the combined blocking effect will be additive. This concept was subjected to experimental verification. Three models namely isolated, spontaneously beating guinea-pig atrium, isolated guinea-pig trachea and in vivo experiments using anaesthetized rats were used. Concentration/dose-response curves were established in all models. lsoprenaline as agonist and various beta receptor antagonists were used in the study. Dose ratio resulting from the shift of agonist curve was obtained for an individual antagonist. When two antagonists were added in combination, dose ratio for the combination was obtained. This experimentally derived dose ratio due to combination of antagonists was compared with the one expected on the theory. In isolated atrium model the dose ratio study revealed that in case of 2 pairs viz. (i) pindolol & labetalol and (ii) sotalol & labetalol the dose ratios with combination of antagonists were infra-additive. With other pairs additive effect was seen. With one pair supra-additive effect was noted. In case of tracheal tissue metoprolol & labetalol resulted into infra-additive effect and combination of labetalol & propranolol resulted into supra-additive effect. In In vivo experiments dose ratio study exhibited infra-additive effect with two pairs viz. (i) sotalol & labetalol and (ii) sotalol and metoprolol. Additive effect was seen with other two pairs. In rats treated with sotalol chronically dose ratios obtained with labetalol and metoprolol were very low indicating infra-additive effect. The results obtained in the study are not in accord with theory of competitive antagonism. Though it is difficult to explain these results, it is suggested that effects observed could arise if the beta blockers are considered to be metaffinoid rather than competitive antagonist. Thus the study provides evidence against considering beta blockers as pure competitive antagonists.


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