Effects of thymoxamine and its metabolites on clonidine-induced hypotension and bradycardia in rats.
Thymoxamine and deacetylthymoxamine antagonized the hypertensive response of pithed rats to noradrenaline and clonidine, probably by inhibiting vascular post-synaptic alpha-adrenoceptors. N-demethyl-deacetylthymoxamine was inactive. Clonidine-induced reduction of tachycardia caused by electrical stimulation of the cardiac sympathetic nerve in pithed rats was antagonized by phentolamine but not by prazosin, thymoxamine, deacetylthymoxamine or N-demetyldeacetylthymoxamine. This suggests that prazosin and thymoxamine and its derivatives predominantly blocked alpha 1-adrenoceptors. In pentobarbitone-anaesthetized normotensive rats, prazosin, thymoxamine and deacetylthymoxamine decreased the hypotensive effect of clonidine, but had no significant effect on clonidine-induced bradycardia. These substances antagonized clonidine-induced hypotension in rats by the probable mechanism of inhibiting central alpha 1-adrenoceptors whose characteristics are similar to peripheral receptors. These data suggest that clonidine produced a hypotensive action in pentobarbitone anaesthetized rats via alpha 1-adrenoceptors and produced bradycardia via alpha 2-adrenoceptors.
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001919:Bradycardia / Q000139:chemically induced; D003000:Clonidine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D013948:Moxisylyte / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000502:physiology
D003000:Clonidine; D013948:Moxisylyte; D009638:Norepinephrine; D011224:Prazosin