Peers E M, Rance M J, Barnard E A, Haynes A S, Smith C F
Life Sci. 1983;33 Suppl 1:439-42. doi: 10.1016/0024-3205(83)90536-2.
The potential photoaffinity ligand 14-beta-(o-nitro, p-azido)-cinnamoyl-amino-N-cyclopropylmethylnormorphinone (NAM) and its derivative NOM, lacking the p-azido function, were synthesised and their opiate receptor activity determined in isolated tissue preparations. The ligands showed slow receptor kinetics. NAM was a pure competitive antagonist of met5-enkephalin responses in MVD while its antagonism of normorphine responses in GPI appeared non-competitive and non-reversible. In radioligand binding assays NOM completely and irreversibly blocked specific binding of 3H-DHM. Partial blockade of 3H-DADL specific binding was reversible by washing. No binding of NOM to kappa sites was observed. The slow receptor kinetics of NAM preclude its use as a photoaffinity ligand but suggest that a chemically more stable derivative may have a role as a pseudocovalent blocker of mu-receptors.
合成了潜在的光亲和配体14-β-(邻硝基，对叠氮基)-肉桂酰氨基-N-环丙基甲基去甲吗啡酮（NAM）及其缺乏对叠氮基功能的衍生物NOM，并在离体组织制剂中测定了它们的阿片受体活性。这些配体表现出缓慢的受体动力学。NAM是中脑导水管周围灰质中met5-脑啡肽反应的纯竞争性拮抗剂，而其对苍白球内侧核中去甲吗啡反应的拮抗作用似乎是非竞争性和不可逆的。在放射性配体结合试验中，NOM完全且不可逆地阻断了3H-DHM的特异性结合。通过洗涤可使3H-DADL特异性结合的部分阻断逆转。未观察到NOM与κ位点的结合。NAM缓慢的受体动力学使其无法用作光亲和配体，但表明化学性质更稳定的衍生物可能具有作为μ受体假共价阻断剂的作用。
