Summary We compared various imidazoline derivatives with noradrenaline and methoxamine for vasoconstrictor activity in several different vascular beds. We used rat autoperfused hindquarters, kidneys, and mesenteric vasculature; rat saline-perfused renal and mesenteric vasculature; rabbit autoperfused kidneys and hindquarters; and pithed rats and autoperfused rabbit kidneys; and we studied the blood pressure of conscious, ganglion-blocked rabbits. Clonidine, oxymetazoline, naphazoline, St 91, St 95, methoxamine, and nor-adrenaline all acted as full pressor agonists in the pithed rat without any sign of α-antagonist effect. St 91 and noradrenaline were the most potent, and clonidine and methoxamine were the weakest agonists. However, while noradrenaline and methoxamine displayed full vasoconstrictor agonist potencies in the rat autoperfused tissues, all the imidazoline derivatives except St 91 acted as partial agonists or antagonists. St 91 in most cases acted as a full agonist, although in the autoperfused hindquarters it was often a partial agonist. Similar effects were seen in rat saline-perfused tissues, except that antagonists activity was even more prominent. pA2 values for several imidazolidine derivatives were calculated in rat saline-perfused mesenteric and renal vascular beds, and it was found that oxymetazoline was a considerably more potent α-antagonist than either piperoxane or yohimbine, while clonidine had a similar potentcy to these drugs. In the conscious, ganglion-blocked rabbit, both clonidine and oxymetazoline acted as fairly weak partial agonists, and in the rabbit autoperfused hindquarters and kidneys, clonidine acted as a pure α-antagonist. These results suggest that vascular α-adrenoceptors comprise an heterogeneous population, but the observations may also be due to low receptor reserves in different tissues.
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Hepburn et al. (1982) studied this question.