title: Postsynaptic alpha 1- and alpha 2-adrenoceptor blocking properties of (dihydro)quinidine and (dihydro)quinine.
abstract: The antagonistic properties of the cinchona alkaloids quinidine, dihydroquinidine, quinine and dihydroquinine were evaluated with respect to alpha 1- and alpha 2-adrenoceptor-induced vasoconstriction in pithed normotensive rats. Radioligand displacement studies were performed to determine the in vitro affinities of the alkaloids for alpha 1- and alpha 2-adrenoceptors. Quinidine and dihydroquinidine were more effective alpha 1-adrenoceptor antagonists than quinine and dihydroquinine. Their weak to moderate alpha 1-sympatholytic activities were compatible with their in vitro affinity for alpha 1-adrenoceptors. The potencies of (dihydro)quinidine and (dihydro)quinine in inhibiting vascular postsynaptic alpha 2-adrenoceptor-mediated pressor effects were also weak and comparable in the lower dose range (15-250 mumol kg-1). In a dose of 300 mumol kg-1, dihydroquinidine exceeded the other alkaloids in activity. The alpha 2-adrenoceptor antagonistic actions of the alkaloids did not correspond with their actual affinity for alpha 2-adrenoceptors observed in vitro. A calcium antagonistic action is proposed to contribute to the interference of these drugs with the vasoconstriction governed by alpha 2-adrenoceptors. The interaction of quinine, quinidine and their hydrogenated products with vascular alpha 1- and alpha 2-adrenoceptors may explain their hypotensive properties as well as their therapeutic effect in certain forms of vascular disorders.
mesh_terms: D000317:Adrenergic alpha-Antagonists; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D011802:Quinidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013569:Synapses / Q000187:drug effects
chemical_list: D000317:Adrenergic alpha-Antagonists; D001381:Azepines; C024763:talipexole; C014486:hydroquinidine; D008729:Methoxamine; D011802:Quinidine