Pre- and postsynaptic alpha-adrenoceptor blocking properties of a new dihydrobenzofurane derivative (imidazolinyl-2)-2-dihydro 2,3 benzofurane (S 9871) and its stereoisomers in rats.
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.
D000317:Adrenergic alpha-Antagonists; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001572:Benzofurans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D014649:Vas Deferens / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D001381:Azepines; D001572:Benzofurans; D007093:Imidazoles; D010656:Phenylephrine; C042254:S 9871; C015603:azepexole; D003000:Clonidine; C014282:cirazoline