Gibson R E, Moody T, Schneidau T A, Jagoda E M, Reba R C
Department of Radiology, George Washington University Medical Center, Washington, D.C. 20037.
Life Sci. 1992;50(9):629-37. doi: 10.1016/0024-3205(92)90249-o.
We have determined the kinetics of dissociation of (R)-3-Quinuclidinyl (R)-4-[125I]Iodobenzilate ((R,R)-[125I]4IQNB) from muscarinic acetylcholine receptor preparations from the cortex, hippocampus, caudate/putamen, thalamus, pons and colliculate bodies. The dissociation curves are well described by a biexponential function and are consistent with subtype selectivity favoring slow dissociation from the M1, M3, and M4 receptors with a 20-fold faster dissociation rate for the M2 receptor. Following intravenous injection, (R,R)-[125I]4IQNB binds to receptor in the rat brain in concentrations which reflect the receptor concentration present in a structure. We determined the extent of radioligand present at two times, 2 and 24 hrs, as an indication of the relative proportions of m-AChR which exhibits rapid vs. slow dissociation of (R,R)-[125I]4IQNB. A good correlation between in vitro and in vivo results suggests that the relative populations of receptor subtypes can be imaged using in vivo pharmacokinetics of (R,R)-[125I]4IQNB.
我们已经测定了（R）-3-奎宁环基（R）-4-[125I]碘苄酸盐（（R，R）-[125I]4IQNB）从皮质、海马体、尾状核/壳核、丘脑、脑桥和丘状体的毒蕈碱型乙酰胆碱受体制剂上解离的动力学。解离曲线可用双指数函数很好地描述，并且与亚型选择性一致，即有利于从M1、M3和M4受体缓慢解离，而M2受体的解离速率快20倍。静脉注射后，（R，R）-[125I]4IQNB以反映某一结构中受体浓度的浓度与大鼠脑中的受体结合。我们测定了在2小时和24小时这两个时间点存在的放射性配体的量，以此作为显示（R，R）-[125I]4IQNB快速与缓慢解离的毒蕈碱型乙酰胆碱受体相对比例的指标。体外和体内结果之间的良好相关性表明，使用（R，R）-[125I]4IQNB的体内药代动力学可以对受体亚型的相对群体进行成像。
