N-[4-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)butyl]-2-methoxy-5-methyl-benzamide (RHM-1) and N-[2-(3,4-dihydro-6,7-dimethoxyisoquinolin-2(1H)-yl)ethyl]-2-methoxy-5-methylbenzamide (RHM-2), two conformationally flexible benzamide analogues, were radiolabeled with tritium (specific activity=80 Ci/mmol) and the binding of [3H]RHM-1 and [3H]RHM-2 to sigma-2 (sigma2) receptors was evaluated in vitro. [3H]RHM-1 was found to have a higher affinity for sigma2 receptors compared to [3H]RHM-2 and [3H]1,3-di-o-tolylguanidine ([3H]DTG). [3H]RHM-1 had a dissociation constant (Kd) of 0.66+/-0.12 nM in rat liver membrane homogenates, which was 30-fold higher than that of [3H]RHM-2 (Kd=19.48+/-0.51 nM). The lower affinity of [3H]RHM-2 can be attributed to its faster K(off) rate since both radioligands have similar K(on) rates. Competitive binding assays were also conducted using a panel of compounds with known affinity for sigma2 receptors. The pharmacologic profile of [3H]RHM-1 was in agreement with that of [3H]DTG. The results of this study indicate that [3H]RHM-1 is a useful ligand for studying sigma2 receptors in vitro.

中文翻译：

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[3H] N- [4-（3,4-二氢-6,7-二甲氧基异喹啉-2（1H）-基）丁基] -2-甲氧基-5-甲基苯甲酰胺：新型sigma-2受体探针。

N- [4-（3,4-二氢-6,7-二甲氧基异喹啉-2（1H）-基）丁基] -2-甲氧基-5-甲基苯甲酰胺（RHM-1）和N- [2-（3 two具有放射性构象的两个构象灵活的苯甲酰胺类似物1,4-二氢-6,7-二甲氧基异喹啉-2（1H）-基）乙基] -2-甲氧基-5-甲基苯甲酰胺（RHM-2）（比活度= 80 Ci / mmol），并在体外评估[3H] RHM-1和[3H] RHM-2与sigma-2（sigma2）受体的结合。与[3H] RHM-2和[3H] 1,3-二-邻甲苯基胍（[3H] DTG）相比，发现[3H] RHM-1对sigma2受体具有更高的亲和力。[3H] RHM-1在大鼠肝膜匀浆中的解离常数（Kd）为0.66 +/- 0.12 nM，比[3H] RHM-2的解离常数（Kd = 19.48 +/- 0.51 nM）高30倍）。[3H] RHM-2的较低亲和力可归因于其更快的K（off）速率，因为两个放射性配体的K（on）速率相似。还使用一组对sigma2受体具有已知亲和力的化合物进行竞争性结合测定。[3H] RHM-1的药理特性与[3H] DTG的一致。这项研究的结果表明[3H] RHM-1是用于研究sigma2受体的有用配体。