Ruffolo R R, Messick K, Horng J S
J Auton Pharmacol. 1985 Mar;5(1):71-9. doi: 10.1111/j.1474-8673.1985.tb00567.x.
The activities of a series of dimethoxy-substituted tolazoline derivatives were investigated at alpha 1-adrenoreceptors in guinea-pig aorta and alpha 2-adrenoreceptors in field-stimulated guinea-pig ileum. Radioligand binding studies to alpha 1- and alpha 2-adrenoreceptors in rat cerebral cortex were also performed to support the pharmacological findings. The 2,5- and 3,5-dimethoxy-substituted tolazoline derivatives were potent full agonists at alpha 1-adrenoreceptors in guinea-pig aorta, whereas the 2,3- and 3,4-dimethoxy-substituted tolazoline derivatives were inactive as alpha 1-adrenoreceptor agonists. 2,3-Dimethoxytolazoline was a partial agonist at alpha 2-adrenoreceptors in field-stimulated guinea-pig ileum. The intrinsic activity of 2,3-dimethoxytolazoline was similar to that of clonidine, but less than that of UK-14,304. The -log ED50 of 2,3-dimethoxytolazoline (7.66) was only 3- to 5-fold lower than that of clonidine or UK-14,304, indicating that this compound has relatively high potency as an alpha 2-adrenoreceptor agonist. The 2,5-, 3,5- and 3,4-dimethoxy-substituted tolazoline derivatives were inactive as alpha 2-adrenoreceptor agonists. 3,4-Dimethoxytolazoline was a moderately potent and selective alpha 2-adrenoreceptor antagonist in field-stimulated guinea-pig ileum. The results indicate that the dimethoxy-substituted tolazoline derivatives possess different pharmacological activities and selectivities at alpha 1- and alpha 2-adrenoreceptors, depending upon the positions of the dimethoxy substitutions. The 2,5- and 3,5-dimethoxytolazoline derivatives are potent and selective alpha 1-adrenoreceptor agonists, whereas 2,3-dimethoxytolazoline is a potent and selective alpha 2-adrenoreceptor agonist. 3,4-dimethoxytolazoline is a moderately potent and selective alpha 2-adrenoreceptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了一系列二甲氧基取代的妥拉唑啉衍生物对豚鼠主动脉α1 - 肾上腺素能受体及对电场刺激的豚鼠回肠α2 - 肾上腺素能受体的活性。还进行了对大鼠大脑皮层α1和α2 - 肾上腺素能受体的放射性配体结合研究，以支持药理学研究结果。2,5 - 和3,5 - 二甲氧基取代的妥拉唑啉衍生物是豚鼠主动脉α1 - 肾上腺素能受体的强效完全激动剂，而2,3 - 和3,4 - 二甲氧基取代的妥拉唑啉衍生物作为α1 - 肾上腺素能受体激动剂无活性。2,3 - 二甲氧基妥拉唑啉是电场刺激的豚鼠回肠α2 - 肾上腺素能受体的部分激动剂。2,3 - 二甲氧基妥拉唑啉的内在活性与可乐定相似，但低于UK - 14,304。2,3 - 二甲氧基妥拉唑啉的-log ED50（7.66）仅比可乐定或UK - 14,304低3至5倍，表明该化合物作为α2 - 肾上腺素能受体激动剂具有相对较高的效力。2,5 - 、3,5 - 和3,4 - 二甲氧基取代的妥拉唑啉衍生物作为α2 - 肾上腺素能受体激动剂无活性。3,4 - 二甲氧基妥拉唑啉是电场刺激的豚鼠回肠中一种中等效力且选择性的α2 - 肾上腺素能受体拮抗剂。结果表明，二甲氧基取代的妥拉唑啉衍生物在α1和α2 - 肾上腺素能受体上具有不同的药理活性和选择性，这取决于二甲氧基取代的位置。2,5 - 和3,5 - 二甲氧基妥拉唑啉衍生物是强效且选择性的α1 - 肾上腺素能受体激动剂，而2,3 - 二甲氧基妥拉唑啉是强效且选择性的α2 - 肾上腺素能受体激动剂。3,4 - 二甲氧基妥拉唑啉是一种中等效力且选择性的α2 - 肾上腺素能受体拮抗剂。（摘要截短至250字）
