The early proposals that pre- and post-junctional α-adrenoceptors might be different stemmed largely from two separate observations. Firstly, the orders of potency of a series of agonists at inhibiting the response to sympathetic nerve stimulation and in increasing inotropic activity in the rabbit isolated heart were different [1, 2]. Secondly, phenoxybenzamine was more potent in inhibiting vasoconstrictor responses to sympathetic nerve stimulation than in increasing transmitter overflow from the cat spleen . These experiments illustrate the most fundamental, pharmacological ways of distinguishing between receptors: namely, by comparing the relative potencies of agonists and/or antagonists in producing, or preventing, pharmacological effects.
There are, however, difficulties in using agonists to classify receptors because their ability to generate a response depends not only upon their intrinsic properties of affinity for, and efficacy at, the receptors but also upon the capacity of the tissue to translate the stimulus into a response. Thus agonists with a relatively low intrinsic efficacy may produce a small response, or no response at all, in a tissue in which the efficiency of the stimulus-response coupling mechanism is low. The importance of this phenomenon in influencing tissue responses to agonists with low efficacy has been demonstrated for the α-adrenoceptor agonist prenalterol  and for the α-adrenoceptor agonist oxymetazoline .