Christopher B. Chapleo

Effect of 1,4-dioxanyl substitution on the adrenergic activity of some standard α-adrenoreceptor agents

Abstract A preliminary communication reported on the pharmacology of the potent partial α2-agonist (2-(1,4-benzodioxan-6-ylamino)-2-imidazoline, a 1,4-dioxan derivative of clonidine. Its degree of agonism/antagonism depended upon the peripheral or central α2-adrenoreceptor system studied. It was of interest to discover whether a similar substitution of the 1,4-dioxan moiety in other standard α-adrenergic agents would similarly produce high affinity compounds of complex pharmacological profile. The same substitution when introduced into guanfacine, fenmetazole and tolazoline resulted in unpredictable changes in profile with a reduction in α-affinity.

2-[2-(1,4-benzodioxanyl) ]-2-imidazoline hydrochloride

Abstract A new synthesis of 2-[2-(1,4-benzodioxanyl)]-2-imidazoline hydrochloride from 2-cyano-benzodioxan is described and the previously claimed route to this compound is shown to give a formula isomer, ie. 2-methyl-2-[2-(1,3-benzodioxolyl)]-2-imidazoline hydrochloride.

Comparison of the α-adrenoceptor profiles of clonidine and two oxygenated arylamino imidazolines

The profiles of 2-(3,4-dimethoxyphenylamino)-imidazoline HCl (RX 77171) and 2-[6-(1,4-benzodioxanylamino)]imidazoline maleate (RX 801074) were compared with that of clonidine in isolated tissues and pithed rats. RX 77171 consistently displayed prejunctional α2-adrenoceptor antagonist and postjunctional agonist properties. In contrast, RX 801074 had a complex profile which showed considerable variability between tissues. This variability is highlighted by comparing its effects at the prejunctional α2-adrenoceptors of the isolated vas deferens and guinea-pig ileum; in the former RX 801074 was an agonist whereas only antagonist properties were apparent in the ileum.