The mechanism of action of 2‐halogenoethylamines at the adrenergic α‐receptor and a further investigation of the “spare receptor” hypothesis

The evidence for “spare‐receptors” has been examined in the adrenergic α‐receptor system of the rat vas deferens using N‐(2‐bromoethyl)‐N‐ethyl‐l‐naphthylmethylamine (SY.28) and NN‐dimethyl‐2‐phenylethylamine hydrobromides as the antagonist species. It is clearly demonstrated that “spare‐receptors” are not present in this tissue and that the observed parallel shift of the dose‐response curve of noradrenaline produced by SY.28 is due to a competitive reversible phase of action of the corresponding ethyleneimine species rather than to the presence of “spare‐receptors”. Additionally, these experiments have revealed the existence of a significant non‐competitive reversible phase of action of SY.28. From radiochemical studies and the observed first order recovery of tissue response following blockade by NN‐dimethyl‐2‐bromo‐2‐phenylethylamine, it is concluded that the α‐receptors in the rat vas deferens are indistinguishable from the α‐receptors in the rabbit aorta in their behaviour towards this agent. From these results and those of others, it may be concluded that there is no existing evidence for “spare receptors” in adrenergic α‐receptor systems. 1969 Royal Pharmaceutical Society of Great Britain