EFFECTS OF THE HISTAMINE H2-RECEPTOR BLOCKING-DRUGS BURIMAMIDE AND CIMETIDINE ON NORADRENERGIC TRANSMISSION IN THE ISOLATED AORTA OF THE RABBIT AND ATRIA OF THE GUINEA-PIG

In rabbit aortic strips, concentration‐response curves to noradrenaline (NA) were shifted to the right in a parallel and concentration‐dependent manner by the α‐adrenoceptor blocking drug, phentolamine and also by the histamine H2‐receptor blocking drugs, burimamide and cimetidine. Responses to 5‐hydroxytryptamine were not affected by these drugs. Burimamide had the properties of a competitive antagonist of noradrenaline, possessing about one‐hundredth the potency of phentolamine. Cimetidine was weaker than burimamide and did not fulfil the requirements for competitive antagonism of noradrenaline. In guinea‐pig isolated atria, in which noradrenergic transmitter stores were labelled with [3H]‐noradrenaline, phentolamine (3 μm), burimamide (30 μm) and cimetidine (30 μm), in decreasing order of effectiveness, each enhanced stimulation‐induced efflux of [3H]‐noradrenaline, indicating that their blocking effects on prejunctional α‐adrenoceptors in this tissue are in the same order of relative potency as on postjunctional α‐adrenoceptors in rabbit aortic strips. In the concentrations used (30 μm), neither burimamide nor cimetidine interfered with the neuronal uptake of noradrenaline. Burimamide, and to a much lesser extent, cimetidine, increased the resting efflux of [3H]‐noradrenaline from guinea‐pig atria. The effect of clonidine, a partial agonist on prejunctional α‐adrenoceptors in guinea‐pig atria, in increasing stimulation‐induced efflux of [3H]‐noradrenaline when stimulated with 150 pulses at 5 Hz was blocked by cimetidine (30 μm) and reversed by phentolamine (3 μm) and burimamide (30 μm). 1979 British Pharmacological Society