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In pentobarbital-treated dogs and rats, AR-C239, a new and potent alpha-adrenoceptor blocking drug, competitively antagonized pressor responses to adrenaline and inhibited pressor responses to noradrenaline, phenylephrine, tyramine, and dimethylphenylpiperazinium. Injected intravenously into closed-chest dogs, AR-C239 (3-50 micrograms/kg) induced a progressive fall in blood pressure, heart rate, and sympathetic nerve activity. The drug appears to be devoid of direct vasodilator action, and the fall in blood pressure results from the peripheral alpha-blockade. AR-C239 did not change the tachycardia induced by stimulation of the cardiac nerve in dogs and, at least in this preparation, seems to be a specific alpha 1-adrenoceptor blocking drug. When administered into the cisterna magna of dogs, AR-C239 did not have any centrally mediated cardiovascular actions and heart rate. AR-C239 did not modify the functioning of the baroreflex arc. Due to its specificity for alpha 1-Adrenoceptors, AR-C239 may be useful for characterizing alpha-adrenoceptors.

In dogs anaesthetized with pentobarbital (30 mg. kg -1 i.v.), clonidine (0,01 mg.kg-1 i.v.) reduced the tachycardia induced at low frequencies by stimulation of the cardiac nerve. The effects of some alpha-adrenoceptor blocking agents on this effect have been studied. Small doses of yohimbine (0.3 mg. kg-1 i.v.) or piperoxan (0.3 mg. kg-1 i.v.) increased the effects of the stimulation and in addition antagonized the inhibitory effects of clonidine and reversed the pressor response to adrenaline. Thymoxamine (1 mg.kg-1 i.v.) and prazosin (1 mg.kg-1 i.v.) did not increase the effect of the stimulation of the cardiac nerve, but reduced the effect of clonidine. ARC239 (0.05 mg.kg-1) reversed the pressor response to adrenaline but even at high doses did not increase the effects of the stimulation of the cardiac nerve or the effects of clonidine. These observations afford further evidence for a dissimilarity between pre and post-synaptic alpha-adrenoceptors.

In the present investigation, the alpha-adrenoceptor blocking effect of (imidazolinyl-2)-2-dihydro 2,3 benzofurane or S 9871 and its stereoisomers was studied. In the pithed rat (+/-) and (+) S 9871 competitively antagonized the pressor effects of azepexole and clonidine more effectively than those of cirazoline and phenylephrine. (-) S 9871 only blocked the pressor response of the alpha 1-agonists used: phenylephrine and cirazoline. (+/-) and (+) S 9871 antagonized the inhibitory effects of clonidine on the increase in heart rate produced by stimulation of the sympathetic efferent fibres of the thoracic spinal cord. (-) S 9871 was twenty times less potent on the decrease in heart rate induced by clonidine. On the vas deferens of the rat, (+/-) and (+) S 9871 appeared to be more potent than (-) S 9871 in antagonizing the inhibitory effects of clonidine on the twitch response produced by electrical stimulation. Therefore, (+/-) and (+) S 9871 appear to be more preferential for alpha 2-adrenoceptors than for alpha 1-adrenoceptors; in contrast (-) S 9871 appears to be selective for alpha 1-adrenoceptors. (+/-) and (+) S 9871 appears to be one of the most selective agents for blocking alpha 2-adrenoceptors.