School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Bioorg Med Chem Lett. 2010 Nov 1;20(21):6302-5. doi: 10.1016/j.bmcl.2010.08.083. Epub 2010 Aug 21.
We have reported previously the novel δ-opioid agonist, SN-28, which was more potent in in vitro assays than the prototype δ-agonists, TAN-67 and SNC-80. However, when administered by subcutaneous injection, this compound showed no analgesic effect at dosages greater than 30mg/kg in the acetic acid writhing test. We speculated that SN-28 was not effective in the test because the presence of the charged ammonium groups prevented its penetration through the blood-brain barrier. On the basis of our proposal, we designed the novel δ-agonist, KNT-127, which was effective with systemic administration.
我们之前曾报道过一种新型的 δ 阿片类激动剂 SN-28，它在体外试验中的效力强于原型 δ 激动剂 TAN-67 和 SNC-80。然而，当通过皮下注射给予时，该化合物在醋酸扭体试验中，剂量大于 30mg/kg 时没有显示出镇痛效果。我们推测 SN-28 在测试中无效，是因为带电荷的铵基团的存在阻止了它穿透血脑屏障。基于我们的提议，我们设计了新型的 δ 激动剂 KNT-127，它可以通过系统给药发挥作用。
