Flamez A, De Backer J P, Czerwiec E, Ladure P, Vauquelin G
Protein Chemistry Laboratory, Vrije Universiteit Brussel, Sint-Genesius-Rode, Belgium.
Neurochem Int. 1997 Jan;30(1):25-9. doi: 10.1016/s0197-0186(96)00040-x.
[3H]RX821002, [3H]clonidine and [3H]idazoxan have previously been shown to selectively label alpha 2-adrenergic receptors, I1 and I2 imidazoline receptors in the human central nervous system, respectively. Idazoxan shows relatively high affinity for all three receptors. We investigated the possible selectivity of several compounds towards one of those receptors in human striatum. Addition of an alkoxy group at the 2-position of the benzodioxan moiety of idazoxan (ethoxy-idazoxan, methoxy-idazoxan) increases the alpha 2-selectivity in human brain. Efaroxan is also alpha 2-selective. On the contrary, BU224, BU239, cirazoline and RX801077 display imidazoline receptor selectivity. Our results indicate that for all molecules tested, idazoxan and 'flat' analogs possess I1/I2 receptor selectivity. A 'bulky' substituent at the 2-position of the benzodioxan ring gives rise to alpha 2-adrenergic receptor selectivity. Until now, we found no more than 3-fold difference in IC50 between both imidazoline receptors. Both receptors also display similar stereoselectivity, suggesting that they might be 'interconnected' in the human striatum.
[3H]RX821002、[3H]可乐定和[3H]咪唑克生此前已被证明可分别选择性标记人中枢神经系统中的α2 - 肾上腺素能受体、I1和I2咪唑啉受体。咪唑克生对所有这三种受体均显示出相对较高的亲和力。我们研究了几种化合物对人纹状体中这些受体之一的可能选择性。在咪唑克生的苯并二恶烷部分的2 - 位添加烷氧基（乙氧基 - 咪唑克生、甲氧基 - 咪唑克生）可增加其在人脑中的α2选择性。依酚氯铵也是α2选择性的。相反，BU224、BU239、可乐亭和RX801077表现出咪唑啉受体选择性。我们的结果表明，对于所有测试的分子，咪唑克生及其“扁平”类似物具有I1/I2受体选择性。苯并二恶烷环2 - 位的“庞大”取代基产生α2 - 肾上腺素能受体选择性。到目前为止，我们发现两种咪唑啉受体之间的IC50差异不超过3倍。这两种受体还表现出相似的立体选择性，表明它们在人纹状体中可能“相互关联”。
