Motulsky H J, Maisel A S, Snavely M D, Insel P A
Circ Res. 1984 Sep;55(3):376-81. doi: 10.1161/01.res.55.3.376.
Although quinidine is known to have antiadrenergic effects in the cardiovascular system, the precise mechanism by which it exerts these effects is not well defined. We asked whether quinidine binds directly to adrenergic receptors. Radioligand-binding assays were used to identify alpha 1-adrenergic receptors [( 3H]prazosin-binding sites) on membranes prepared from rat heart and kidney, alpha 2-adrenergic receptor [( 3H]yohimbine-binding sites) on human platelets and rat kidney membranes, and beta-adrenergic receptors [( 125I]iodocyanopindolol-binding sites) on rat heart and kidney membranes. Although it did not effectively compete for binding to beta-adrenergic receptors, quinidine competed for binding to alpha 1- and alpha 2-adrenergic receptors and yielded equilibrium dissociation constants of 0.3-3 microM. Two other antiarrhythmic agents, lidocaine and procainamide, did not compete for binding to alpha-adrenergic receptors. Further experiments demonstrated that the interactions of quinidine with the cardiac alpha 1- and platelet alpha 2-adrenergic receptors were competitive and reversible. We conclude that that antiadrenergic actions of quinidine can be explained by occupancy and competitive blockade of alpha 1- and alpha 2-adrenergic receptors.
尽管已知奎尼丁在心血管系统中具有抗肾上腺素能作用，但其发挥这些作用的确切机制尚不清楚。我们研究了奎尼丁是否直接与肾上腺素能受体结合。采用放射性配体结合试验来鉴定大鼠心脏和肾脏制备的膜上的α1肾上腺素能受体（[3H]哌唑嗪结合位点）、人血小板和大鼠肾脏膜上的α2肾上腺素能受体（[3H]育亨宾结合位点）以及大鼠心脏和肾脏膜上的β肾上腺素能受体（[125I]碘氰吲哚洛尔结合位点）。尽管奎尼丁不能有效竞争与β肾上腺素能受体的结合，但它能竞争与α1和α2肾上腺素能受体的结合，其平衡解离常数为0.3 - 3微摩尔。另外两种抗心律失常药物利多卡因和普鲁卡因胺则不能竞争与α肾上腺素能受体的结合。进一步的实验表明，奎尼丁与心脏α1和血小板α2肾上腺素能受体的相互作用是竞争性且可逆的。我们得出结论，奎尼丁的抗肾上腺素能作用可通过占据并竞争性阻断α1和α2肾上腺素能受体来解释。
