Pre- and postjunctional effects of clonidine- and oxymetazoline-like compounds in guinea-pig ileal preparations.

1 Noradrenaline and 28 imidazolidine (clonidine-like) and imidazoline (oxymetazoline-like) compounds with various phenyl ring substituents have been examined for their ability to inhibit responses to transmural stimulation and exogenous acetylcholine in ileal preparations from reserpine-treated guinea-pigs.2 The bathing solution contained propranolol, mepyramine, cimetidine and desipramine to preclude interference with the responses by other than the alpha-receptor-mediated actions of the compounds.3 In transmurally stimulated preparations the inhibitory response to noradrenaline is due to a combination of prejunctional alpha-adrenoceptor stimulation and a postjunctional depressant effect that does not involve adrenoceptor activation.4 Of the 28 imidazolidines and imidazolines studied, 21 inhibited transmurally elicited responses. In the various compounds studied this effect involved actions at pre- or postjunctional sites as indicated by (a) the frequency-dependence of the inhibitory response, (b) its susceptibility to blockade by alpha-receptor antagonists and (c) the relative concentrations required to inhibit responses to transmural stimulation and exogenous acetylcholine.