氚标记强效镇痛剂N-[1-(β-羟基-β-苯乙基)-3-甲基-4-哌啶基]-N-丙酰苯胺的制备以及与阿片受体的结合试验

本文报道以N-1-(对-溴苯甲酰甲基)-3-甲基-4-哌啶基]-N-丙酰苯胺(Ⅲ)为前体,以PdO/BaSO₄作催化剂,用氚气进行卤—氚置换,氚化还原羰基的反应。反应产物经硅胶纸层析纯化后,用甲基橙比色法定量测定,得到N-{1-β-羟基-β-氚-β-(对-氚苯基)乙基]-3-甲基-4-哌啶基}-N-丙酰苯胺(Ⅳ,³H]F-7302),其比放射性为59 Ci/mM,放化纯度为98%。³H]F-7302与小鼠脑内阿片受体的特异性结合在浓度为4.5×10^-9M时达到饱和,解离常数Kd=1.25×10^-9M,最大结合量B_max=93.08×10¹²M/g蛋白,其特异性结合与非特异性结合比值达10～15。

Preparation of [3H]-labelled N-[1-(beta-hydroxy beta-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropionamide and studies of its binding with opiate receptors of mouse brain

A new potent narcotic analgesic, N-1-(β-hydroxy β-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropionamide (simply named as F-7302) was labelled by tritiumhalogen exchange and catalytic reduction of N-1-(p-bromo-benzoyl methyl)-3-methyl-4-piperidyl]-N-phenylpropionamide with tritium gas, using PdO/BaSO₄ as catalyst, removal of labile tritium by treating with alcohol, and final purification with silica-gel paper chromatography. Methyl orange was employed for the quantitative determination of ³H] F-7302. The specific radioactivity was 59 ci/mM, and the radiochemical purity was 98%.³H] F-7302 binding experiments with opiate receptors of mouse brain showed a high affinity and specificity. The saturation concentration for the stereospecific binding of ³H]F-7302 was 4.5×10^-9M. and the dissociation constant was 1.25×10^-9M.The retio of specific/nonspecific binding was 10～15.