The dipeptide amide H-Phe-Phe-NH₂ (1) that previously was identified as a ligand for the substance P 1–7 (SP_1–7) binding site exerts intriguing results in animal models of neuropathic pain after central but not after peripheral administration. The dipeptide 1 is derived from stepwise modifications of the anti-nociceptive heptapeptide SP_1–7 and the tetrapeptide endomorphin-2 that is also binding to the SP_1–7 site. We herein report a strong anti-allodynic effect of a new H-Phe-Phe-NH₂ peptidomimetic (4) comprising an imidazole ring as a bioisosteric element, in the spare nerve injury (SNI) mice model after peripheral administration. Peptidomimetic 4 was stable in plasma, displayed a fair membrane permeability and a favorable neurotoxic profile. Moreover, the effective dose (ED₅₀) of 4 was superior as compared to gabapentin and morphine that are used in clinic.

二肽酰胺H-Phe-Phe-NH ₂（1）先前被确定为P 1-7（SP _1-7）结合位点的配体，在中枢性神经痛后的动物模型中产生了有趣的结果外围管理。二肽1源自抗伤害感受态七肽SP _1-7和也与SP _1-7位点结合的四肽内啡肽2的逐步修饰。我们在此报告了一种新型H-Phe-Phe-NH ₂拟肽（4在周围给药后的备用神经损伤（SNI）小鼠模型中，含有咪唑环作为生物等位元素的化合物）。拟肽4在血浆中稳定，显示出良好的膜通透性和良好的神经毒性特征。此外，与临床使用的加巴喷丁和吗啡相比，有效剂量（ED ₅₀）为4更好。