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  • Title: Alpha 1- and alpha 2-adrenoceptor selectivity of moxisylyte (thymoxamine) and its metabolites in the pithed rat.
    Author: Roquebert J, Malek A, Creuzet MH, Cognie F, Pontagnier H.
    Journal: Arch Int Pharmacodyn Ther; 1983 Dec; 266(2):282-93. PubMed ID: 6320755.
    Abstract:
    The selectivity of moxisylyte and its two metabolites deacetylmoxisylyte and demethyldeacetylmoxisylyte, for alpha 1- and alpha 2-adrenoceptors has been investigated in the pithed rat. Alpha 2-adrenoceptor blockade was measured by antagonism of the inhibitory effect of clonidine on the tachycardia produced by electrical stimulation of the cardiac accelerator nerves and of the pressor response to B-HT 933. alpha 1-Adrenoceptor blockade was measured by inhibition of the pressor response to (-)phenylephrine and to stimulation of the sympathetic outflow from the spinal cord. The three drugs (5 X 10(-6) to 2 X 10(-5) mol/kg i.v.) did not affect the inhibitory effect of clonidine and were equipotent as antagonists of the pressor response to B-HT 933, but only at the higher dose (10(-5) mol/kg). Moxisylyte and its metabolites (2.5 X 10(-6) to 10(-5) mol/kg i.v.) reduced the pressor response to (-)phenylephrine and to stimulation of the sympathetic outflow of the spinal cord in a dose-dependent manner. They were much more effective against (-)phenylephrine than B-HT 933. These results indicate that the three drugs are preferential alpha 1-adrenoceptor antagonists in vivo.
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