Schoeffter P, Hoyer D
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
Naunyn Schmiedebergs Arch Pharmacol. 1989 Jul;340(1):135-8. doi: 10.1007/BF00169219.
GR 43175 (3-[2-dimethylamino]ethyl-N-methyl-1 H-indole-5 methane sulphonamide) is a novel 5-HT1-like receptor-selective agonist which was reported to be active in the treatment of migraine attacks. The effects of the compound were investigated in radioligand binding studies and in functional models for 5-HT1A, 5-HT1B, and 5-HT1D receptors (inhibition of forskolin-stimulated adenylate cyclase activity in calf hippocampus, rat and calf substantia nigra, respectively) and 5-HT1C receptors (stimulation of inositol phosphate production in pig choroid plexus). GR 43175 displayed the following order of affinity for 5-HT recognition sites (pKD values, -log mol/l, in parentheses): 5-HT1D (7.54) greater than 5-HT1B (6.35) greater than 5-HT1A (6.13) much greater than 5-HT1C (4.13) greater than 5-HT2 (3.67). The same order of potency was observed at functional 5-HT1 receptors, at which GR 43175 acted as a full agonist, with the exception of the 5-HT1C receptor, where the compound was a weak antagonist (pEC50 or pKB values, -log mol/l, in parentheses): 5-HT1D (6.28) greater than 5-HT1B (6.03) greater than 5-HT1A (5.57) much greater than 5-HT1C (4.25). The present data show that GR 43175 interacts preferentially as an agonist with 5-HT1B and 5-HT1D receptors. Since 5-HT1B receptors have not yet been identified in human brain, it seems possible that it is the 5-HT1D receptor which is relevant to the reported antimigraine effects of this compound.
GR 43175（3-[2-二甲基氨基]乙基-N-甲基-1H-吲哚-5-甲磺酰胺）是一种新型的5-HT1样受体选择性激动剂，据报道其在偏头痛发作的治疗中具有活性。在放射性配体结合研究以及5-HT1A、5-HT1B和5-HT1D受体（分别抑制小牛海马体、大鼠和小牛黑质中福斯高林刺激的腺苷酸环化酶活性）和5-HT1C受体（刺激猪脉络丛中肌醇磷酸生成）的功能模型中研究了该化合物的作用。GR 43175对5-HT识别位点的亲和力顺序如下（括号内为pKD值，-log mol/l）：5-HT1D（7.54）大于5-HT1B（6.35）大于5-HT1A（6.13）远大于5-HT1C（4.13）大于5-HT2（3.67）。在功能性5-HT1受体上观察到相同的效价顺序，在这些受体上GR 43175作为完全激动剂起作用，但5-HT1C受体除外，在该受体上该化合物是弱拮抗剂（括号内为pEC50或pKB值，-log mol/l）：5-HT1D（6.28）大于5-HT1B（6.03）大于5-HT1A（5.57）远大于5-HT1C（4.25）。目前的数据表明，GR 43175作为激动剂优先与5-HT1B和5-HT1D受体相互作用。由于在人脑中尚未鉴定出5-HT1B受体，因此似乎有可能是5-HT1D受体与该化合物报道的抗偏头痛作用相关。
