Ruffolo R R, Nichols A J, Patil P N, Hamada A, Clark M, Miller D D
Department of Pharmacology, Smith Kline and French Laboratories, King of Prussia, PA 19406.
Eur J Pharmacol. 1988 Nov 22;157(2-3):235-9. doi: 10.1016/0014-2999(88)90389-5.
The R(-)- and S(+)-enantiomers of alpha-hydroxytolazoline, the benzylic hydroxy-substituted derivative of the alpha-adrenoceptor antagonist, tolazoline, were evaluated at alpha 1- and alpha 2-adrenoceptors in canine saphenous vein. Benzylic hydroxyl substitution of tolazoline in either the R(-) or S(+) configuration significantly decreased affinity at both alpha 1- and alpha 2-adrenoceptors. Differences in affinity between the R(-)- and S(+)-enantiomers were small, which is characteristic of imidazolines, but in marked contrast to phenethylamines where enantiomeric differences are large. The rank order of affinities at alpha 1- and alpha 2-adrenoceptors is tolazoline greater than S(+)-alpha-hydroxytolazoline = R(-)-alpha-hydroxytolazoline, which is different from that order predicted by the Easson-Stedman hypothesis (i.e., R(-) greater than S(+) = desoxy). The findings support our contention that phenethylamines and imidazolines interact differently with alpha-adrenoceptors.
α-羟基妥拉唑啉的R(-)-和S(+)-对映体，即α-肾上腺素能受体拮抗剂妥拉唑啉的苄基羟基取代衍生物，在犬隐静脉的α1-和α2-肾上腺素能受体上进行了评估。无论是R(-)还是S(+)构型的妥拉唑啉的苄基羟基取代均显著降低了对α1-和α2-肾上腺素能受体的亲和力。R(-)-和S(+)-对映体之间的亲和力差异很小，这是咪唑啉类的特征，但与对映体差异很大的苯乙胺类形成鲜明对比。α1-和α2-肾上腺素能受体上的亲和力排序为妥拉唑啉大于S(+)-α-羟基妥拉唑啉 = R(-)-α-羟基妥拉唑啉，这与伊斯特曼-斯特德曼假说预测的顺序（即R(-)大于S(+) = 脱氧）不同。这些发现支持了我们的观点，即苯乙胺类和咪唑啉类与α-肾上腺素能受体的相互作用方式不同。
