Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.
J Med Chem. 2013 Mar 14;56(5):2160-4. doi: 10.1021/jm301872x. Epub 2013 Feb 27.
β-Amino acids sharing a lipophilic diaromatic side chain were synthesized and characterized pharmacologically on mouse GABA transporter subtypes mGAT1-4. The parent amino acids were also characterized. Compounds 13a, 13b, and 17b displayed more than 6-fold selectivity for mGAT2 over mGAT1. Compound 17b displayed anticonvulsive properties inferring a role of mGAT2 in epileptic disorders. These results provide new neuropharmacological tools and a strategy for designing subtype selective GABA transport inhibitors.
β-氨基酸共享亲脂性二芳基侧链被合成并在小鼠 GABA 转运体亚型 mGAT1-4 上进行了药理学表征。还对母体氨基酸进行了表征。化合物 13a、13b 和 17b 对 mGAT2 的选择性超过 mGAT1 达 6 倍以上。化合物 17b 显示出抗惊厥特性，提示 mGAT2 在癫痫疾病中的作用。这些结果提供了新的神经药理学工具和设计亚型选择性 GABA 转运抑制剂的策略。
