Mosberg H I, Hurst R, Hruby V J, Gee K, Akiyama K, Yamamura H I, Galligan J J, Burks T F
Life Sci. 1983;33 Suppl 1:447-50. doi: 10.1016/0024-3205(83)90538-6.
The cyclic, penicillamine(beta, beta dimethylcysteine)-containing enkephalin analogs, [D-Cys2, L-Pen5]-and [D-Cys2, D-Pen5]enkephalin and the corresponding bis-penicillamine analogs, [D-Pen2, L-Pen5]-and [D-Pen2, D-Pen5]enkephalin were synthesized and evaluated for opioid activity in the guinea pig ileum (GPI) and mouse vas deferens (MVD) bioassays and in rat brain and neuroblastoma-glioma cell membrane binding assays. These analogs all displayed delta receptor selectivity as assessed by IC50(GPI)/IC50(MVD) ratios and by their relative potencies for displacing [3H]naloxone (NAL) vs. [3H] [D-Ala2, D-Leu5]enkephalin (DADLE) from rat brain membrane preparations. For [D-Pen2, L-Pen5]- and [D-Pen2, D-Pen5]enkephalin the observed IC50(GPI)/IC50 (MVD) ratios (1088 and 3164) and IC50NAL/IC50DADLE ratios (371 and 175) represent a vast improvement over previously reported delta receptor selective ligands.
合成了含青霉胺（β，β-二甲基半胱氨酸）的环脑啡肽类似物[D-Cys2，L-Pen5]-和[D-Cys2，D-Pen5]脑啡肽以及相应的双青霉胺类似物[D-Pen2，L-Pen5]-和[D-Pen2，D-Pen5]脑啡肽，并在豚鼠回肠（GPI）和小鼠输精管（MVD）生物测定以及大鼠脑和神经母细胞瘤-胶质瘤细胞膜结合测定中评估了它们的阿片样物质活性。通过IC50（GPI）/IC50（MVD）比值以及它们从大鼠脑膜制剂中置换[3H]纳洛酮（NAL）与[3H][D-Ala2，D-Leu5]脑啡肽（DADLE）的相对效力评估，这些类似物均表现出δ受体选择性。对于[D-Pen2，L-Pen5]-和[D-Pen2，D-Pen5]脑啡肽，观察到的IC50（GPI）/IC50（MVD）比值（分别为1088和3164）以及IC50NAL/IC50DADLE比值（分别为371和175）相较于先前报道的δ受体选择性配体有了极大的改进。
