Rothman R B, Bykov V, Reid A, De Costa B R, Newman A H, Jacobson A E, Rice K C
Unit on Receptor Studies, LCS, NIMH, Bethesda, MD 20892.
Neuropeptides. 1988 Oct;12(3):181-7. doi: 10.1016/0143-4179(88)90052-2.
Norbinaltorphimine (nor-BNI) is a bifunctional reagent developed as a selective antagonist of the kappa opioid receptor. In this paper we examined the in vitro selectivity of nor-BNI, 6-desoxy-6 beta-fluoronaltrexone (cycloFOXY), and the enantiomer of cycloFOXY, among opioid receptor subtypes. Nor BNI exhibited the highest affinity for kappa binding sites labeled by 3H-U69593 (Ki = 1.8nM), and was 27- to 29-fold less potent at mu and delta binding sites. In contrast, cycloFOXY had the highest affinity for mu binding sites (Ki = 2.62 nM), and bound to kappa and delta binding sites with Ki's of 9.3 nM and 89 nM, respectively. The enantiomer of cycloFOXY, did not inhibit binding even at concentrations greater than 10 microM, validating in part the use of 18F-labeled (+)-cycloFOXY to estimate "non-specific binding" in positron emission tomography. Additionally, we report that (S,S)-U50 488 and (R.R)-U50 488 bind to kappa binding sites labeled by 3H-U69 593 with Ki's of 0.89 nM and 299 nM, respectively.
去甲纳曲酮啡诺（nor-BNI）是一种开发用作κ阿片受体选择性拮抗剂的双功能试剂。在本文中，我们研究了去甲纳曲酮啡诺、6-脱氧-6β-氟纳曲酮（环FOXY）及其对映体在阿片受体亚型中的体外选择性。去甲纳曲酮啡诺对由3H-U69593标记的κ结合位点表现出最高亲和力（Ki = 1.8 nM），在μ和δ结合位点的效力分别低27至29倍。相比之下，环FOXY对μ结合位点具有最高亲和力（Ki = 2.62 nM），与κ和δ结合位点的结合Ki值分别为9.3 nM和89 nM。环FOXY的对映体即使在浓度大于10 μM时也不抑制结合，这部分验证了在正电子发射断层扫描中使用18F标记的（+）-环FOXY来估计“非特异性结合”。此外，我们报告（S,S）-U50 488和（R,R）-U50 488与由3H-U69 593标记的κ结合位点结合，Ki值分别为0.89 nM和299 nM。
