Manley P W, Quast U, Andres H, Bray K
Preclinical Research Department, Sandoz Pharma Ltd., Basel, Switzerland.
J Med Chem. 1993 Jul 9;36(14):2004-10. doi: 10.1021/jm00066a009.
The synthesis of N-cyano-N'-[1,1-dimethyl-[2,2,3,3-3H]propyl]-N"-(3- pyridinyl)guanidine, [3H]-15, is described. The utility of this tritiated radioligand in characterizing the interactions of potassium channel openers and blockers with their receptors is demonstrated. Potassium channel openers of the pinacidil, cromakalim, aprikalim, diazoxide, and minoxidil types, as well as KATP channel blockers of the glibenclamide and eosine types, are all capable of displacing [3H]-15 from its receptor. The results indicate that all of these compounds interact with the same target protein, but that several different allosterically coupled receptor binding sites are probably involved. The highly significant correlation between the ability of the structurally diverse potassium channel openers to inhibit [3H]-15 binding and to relax vascular smooth muscle is consistent with their receptor binding sites being closely associated with the potassium channel protein which is the functional target of this class of drugs.
本文描述了N-氰基-N'-[1,1-二甲基-[2,2,3,3-³H]丙基]-N"-(3-吡啶基)胍（[³H]-15）的合成。证明了这种氚标记的放射性配体在表征钾通道开放剂和阻滞剂与其受体相互作用方面的效用。匹那地尔、克罗卡林、阿普卡林、二氮嗪和米诺地尔类型的钾通道开放剂，以及格列本脲和曙红类型的KATP通道阻滞剂，都能够从其受体上取代[³H]-15。结果表明，所有这些化合物都与同一靶蛋白相互作用，但可能涉及几个不同的变构偶联受体结合位点。结构多样的钾通道开放剂抑制[³H]-15结合和舒张血管平滑肌的能力之间高度显著的相关性，与它们的受体结合位点与作为这类药物功能靶点的钾通道蛋白密切相关是一致的。
