Alpha 1- and alpha 2-adrenoceptor selectivity of moxisylyte (thymoxamine) and its metabolites in the pithed rat.
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.
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D013948:Moxisylyte / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013116:Spinal Cord / Q000502:physiology
D001381:Azepines; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; C039678:deacetylmoxisylyte; C039679:demethyldeacetylmoxisylyte; C015603:azepexole; D003000:Clonidine; D013948:Moxisylyte