Interactions of MEN 935 (adimolol), a long acting beta- and alpha-adrenolytic antihypertensive agent, with postsynaptic alpha-adrenoceptors in different isolated blood vessels--influence of angiotensin II.

MEN 935 [1-(3-[3-(1-naphthoxy)-2-hydroxypropyl) amino)-3,3-dimethylpropyl)-2-benzimidazolinone-hydrochloride monohydrate, adimolol] is a long acting antihypertensive agent with beta- and alpha-adrenolytic properties. Preliminary experiments in pithed rats had led to the suggestion that the alpha-adrenolytic activity was of the alpha 2-subtype. The alpha-adrenolytic properties of MEN 935 were now tested in isolated vascular preparations of rat aorta, rabbit vena ischiadica and rabbit vena cava inferior against the selective alpha 1-adrenergic agonist phenylephrine (PE) and the selective alpha 2-adrenergic agonist B-HT 920 [2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d)azepine]. The experiments were performed in absence and in presence of 5 X 10(-9) mol/l angiotensin II (A II). MEN 935 antagonized contractions to phenylephrine as well as those to B-HT 920 in each vessel. A twofold shift to the right of the concentration-response curves to both agonists was obtained with concentrations between 1.9 X 10(-8) and 1.4 X 10(-5) mol/l, depending on the vessel under investigation. A II modulated the adrenolytic properties of MEN 935 in each vessel. However, irrespective of the presence or absence of A II, no pharmacologically relevant difference between antagonism against PE or B-HT 920 could be seen. In isolated vessels, MEN 935 exerts a nonselective alpha-adrenergic antagonism. In receptor binding studies in rat cerebellar cortex, MEN 935 showed a Ki of 5.2 X 10(-7) mol/l at alpha 1-adrenoceptors and a Ki of 1.3 X 10(-5) mol/l at alpha 2-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)