The action and interaction of beta-phenethylamines and imidazolines on prejunctional alpha 2-adrenoceptors of guinea-pig ileum in the presence of the non-competitive antagonist benextramine.

The effects of benextramine, a selective non-competitive, irreversible antagonist of alpha-adrenoceptors, against alpha 2-adrenoceptor agonists has been investigated in isolated field-stimulated guinea-pig ileum. Benextramine was equipotent against the imidazoline, clonidine and the thiazoloazepine B-HT920, however, higher concentrations of benextramine were required for an equivalent non-competitive antagonism of the beta-phenethylamine, alpha-methylnoradrenaline. Using benextramine to differentially block the agonist effects of clonidine but not alpha-methylnoradrenaline it was shown that clonidine can competitively antagonize the effects of alpha-methylnoradrenaline. From these and previous results on the differential effects of imidazoline-like and beta-phenethylamine-like drugs on alpha 2-adrenoceptors, it is proposed that two distinct populations of these receptors exist.