Antagonism by propranolol of the inhibitory effect of phenoxybenzamine on noradrenaline uptake in vivo
- 1 December 1971
- journal article
- Published by Oxford University Press (OUP) in Journal of Pharmacy and Pharmacology
- Vol. 23 (12), 911-917
- https://doi.org/10.1111/j.2042-7158.1971.tb09892.x
Abstract
The reduction of noradrenaline stores and [3H]noradrenaline concentration in the heart of mice and rats induced by phenoxybenzamine-treatment, alone or in combination with cold-stress, was prevented by propranolol. Propranolol also antagonized a similar effect induced by phentolamine but not that induced by other noradrenaline uptake inhibitors, such as desipramine, cocaine, guanethidine and reserpine. Analysis of the time-course of antagonism by propranolol indicates that it was evident only when the β-adrenoceptor blocking agent remained in the body. The inhibitory effect of phenoxybenzamine on noradrenaline stores reappeared when propranolol was excreted. Propranolol alone did not change cardiac noradrenaline stores or [3H]noradrenaline. It is concluded that the restoration of reflexly increased adrenergic discharge to normal, because of unmasking of spare α-adrenoceptors resulting from β-adrenoceptor blockade by propranolol rather than competition for binding at the active site of phenoxybenzamine, is responsible for the observed antagonism.Keywords
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