Abstract
The pharmacological properties of thymoxamine hydrochloride (thymoxamine) and its two metabolites, deacetyl-thymoxamine (DAM) and deacetyl-demethyl-thymoxamine (Met-X), were investigated using the isolated smooth muscle preparation. The rank order of potency of competitive α-adrenoceptor blocking action was: phentolamine>thymoxamine≅DAM>Met-X in isolated vas deferens and thoracic aorta spiral strip of rats. The antagonistic effects of thymoxamine, DAM and Met-X against two α-adrenoceptor agonists, norepinephrine or phenylephrine, were competitively in the helically-cut strips of isolated rabbit thoracic aorta, too. It was indicated that thymoxamine and DAM have selective α1-adrenoceptor blocking actions because the antagonistic effects of these drugs were greater to phenylephrine than norepinephrine. Antihistaminic actions of thymoxamine and two metabolites were potencies as well as α-antagonistic effects in isolated guinea-pig ileum. Furthermore, thymoxamine and its metabolites did not have markedly anticholinergic, antiserotonergic and calcium-antagonistic actions. In isolated thoracic aorta strips of rabbit, the K+-induced contractile responses were inhibited by thymoxamine (1×10-4-3×10-4M) at 30-80 %, when non-specific inhibitory effects of thymoxamine did not influence on the cyclic AMP and cyclic GMP contents in vascular tissues.
Those results suggest that pharmacological properties and potencies of DAM have α1-adrenoceptor antagonistic and weak antihistaminic actions as same as thymoxamine.
It was seemed to support that these evidence were able to expect sufficiently the pharmacological actions of thymoxaminein vivo.
