Hudson A L, Chapleo C B, Lewis J W, Husbands S, Grivas K, Mallard N J, Nutt D J
Psychopharmacology Unit, School of Medical Sciences, University of Bristol, U.K.
Neurochem Int. 1997 Jan;30(1):47-53. doi: 10.1016/s0197-0186(96)00037-x.
Using radioligand binding techniques, several compounds selective for mammalian brain imidazoline 2 receptors have been identified. In rabbit brain membranes, a series of 6 and/or 7 aromatic-substituted derivatives of the alpha 2-adrenoceptor antagonist idazoxan were found to show moderate affinity for I2 receptors over alpha 2-adrenoceptors, in particular 6,7-dichloroidazoxan, which was 41 fold selective in favour of I2 receptors. Modification of the benzodioxan ring of idazoxan could also result in affinity and selectivity, which was moderate (2.7 nM, 161 fold) in the case of the 1,3-benzodioxan isomer of idazoxan (2-(1,3-benzodioxanyl)-2-imidazoline), and high (1.3 nM, 2873 fold) in the case of 2-(2-benzofuranyl-2-imidazoline) (2-BFI). Analogues of 2-BFI with halogenic substitutions of the aromatic ring were also found to retain high affinity and moderate to high selectivity for I2-sites. In particular, the 7-chloro (Ki 2.8 nM, 2192 fold) and the 4,6-dibromo (Ki 6.1 nM, 361 fold) analogues of 2-BFI. These new ligands should prove invaluable for investigating the pharmacology and physiology of I2 receptors.
运用放射性配体结合技术，已鉴定出几种对哺乳动物脑咪唑啉2受体具有选择性的化合物。在兔脑膜中，发现α2肾上腺素能受体拮抗剂伊达唑胺的一系列6位和/或7位芳香取代衍生物对I2受体的亲和力高于α2肾上腺素能受体，特别是6,7-二氯伊达唑胺，其对I2受体的选择性为41倍。对伊达唑胺的苯并二恶烷环进行修饰也可产生亲和力和选择性，伊达唑胺的1,3-苯并二恶烷异构体（2-(1,3-苯并二恶烷基)-2-咪唑啉）的亲和力和选择性适中（2.7 nM，161倍），而2-(2-苯并呋喃基-2-咪唑啉)（2-BFI）的亲和力和选择性较高（1.3 nM，2873倍）。还发现具有芳香环卤代取代的2-BFI类似物对I2位点保持高亲和力和中等到高选择性。特别是2-BFI的7-氯类似物（Ki 2.8 nM，2192倍）和4,6-二溴类似物（Ki 6.1 nM，361倍）。这些新配体对于研究I2受体的药理学和生理学应具有重要价值。
