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

Abstract

1 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. 2 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. 3 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. 4 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. 5 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).