Abstract
The relative selectivity of thymoxamine hydrochloride (thymoxamine) and its metabolites, deacetyl-thymoxamine (DAM) and deacetyl-demethyl-thymoxamine (Met-X) were investigated for α1- and α2-adrenoceptors in the isolated main pulmonary arteries of rabbits, compared with prazosin, yohimbine, phentolamine and ifenprodil. Thymoxamine, DAM and Met-X have competitive a-adrenoceptor blocking actions. The rank order of potency of antagonists against norepinephrine was: prazosin>phentolamine>DAM=ifenprodil≅thymoxamine>yohimbine≅Met-X, and that for phenylephrine was: prazosin>phentolamine≅DAM≅thymoxamine>ifenprodil>Met-X>yohimbine. Thymoxamine, DAM, ifenprodil and prazosin inhibited with twitch responses to electrical transmural stimulation dose-dependently, however, yohimbine enhanced the twitch responses. In isotope experiments using of3H-norepinephrine (3H-NE), thymoxamine and its two metabolites, inhibited the contractile responses induced by electrical stimulation without affecting the stimulation-evoked3H-NE efflux. Furthermore, thymoxamine, DAM and Met-X enhanced the clonidine-induced relaxation, but had no affect on the reduction of3H-NE efflux. Therefore, it is suggested that thymoxamine and two meta-bolites, DAM and Met-X, possess selectivity for the α1-adrenoceptor as well as prazosin, differed from ifenprodil, phentolamine and yohimbine.
