Coquelle T, Christensen J K, Banke T G, Madsen U, Schousboe A, Pickering D S
Neuroscience PharmaBiotec Research Center, Department of Pharmacology, The Royal Danish School of Pharmacy, Copenhagen.
Neuroreport. 2000 Aug 21;11(12):2643-8. doi: 10.1097/00001756-200008210-00008.
The lack of subtype-selective compounds for AMPA receptors (AMPA-R) led us to search for compounds with such selectivity. Homoibotenic acid analogues were investigated at recombinant GluR1o, GluR2o(R), GluR3o and GluR1o + 3o receptors expressed in Sf9 insect cells and affinities determined in [3H]AMPA radioligand binding experiments. (S)-4-bromohomoibotenic acid (BrHIBO) exhibited a 126-fold selectivity for GluR1o compared to GluR3o. Xenopus laevis oocytes were used to express functional homomeric and heteromeric recombinant AMPA-R and to determine BrHIBO potency (EC50) at these channels. (R,S)-BrHIBO exhibited a 37-fold selectivity range amongst the AMPA-R. It is hoped that BrHIBO can be used as a lead structure for the development of other subtype-selective compounds.
缺乏针对α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPA-R）的亚型选择性化合物促使我们去寻找具有这种选择性的化合物。我们在 Sf9 昆虫细胞中表达的重组 GluR1o、GluR2o(R)、GluR3o 和 GluR1o + 3o 受体上研究了高异波亭酸类似物，并在 [3H]AMPA 放射性配体结合实验中测定了亲和力。与 GluR3o 相比，(S)-4-溴高异波亭酸（BrHIBO）对 GluR1o 表现出 126 倍的选择性。非洲爪蟾卵母细胞被用于表达功能性同聚体和异聚体重组 AMPA-R，并测定 BrHIBO 在这些通道上的效力（EC50）。(R,S)-BrHIBO 在 AMPA-R 中表现出 37 倍的选择性范围。希望 BrHIBO 能够作为开发其他亚型选择性化合物的先导结构。
