5-HT1 AND 5-HT2 BINDING PROFILES OF THE SEROTONERGIC AGENTS ALPHA-METHYLSEROTONIN AND 2-METHYLSEROTONIN
5-HT1 AND 5-HT2 BINDING PROFILES OF THE SEROTONERGIC AGENTS ALPHA-METHYLSEROTONIN AND 2-METHYLSEROTONIN
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DOI：
10.1021/jm00164a046
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发表时间：
1990-02-01
影响因子：
7.3
通讯作者：
GLENNON, RA
中科院分区：
文献类型：
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作者：
ISMAIEL, AM;TITELER, M;GLENNON, RA
α-甲基-5-羟色胺(α-Me-5-HT；2)和2-甲基-5-羟色胺(2-Me-5-HT；3)分别被认为是5-HT2-选择性剂和5-HT3-选择性剂。这些药物是在血清素 (5-HT) 结合位点合成和检查的，因为有关其选择性的文献相对较少，而且之前没有在新发现的 5-HT1D 和 5-HT1E 位点检查过它们。如先前报道，2-Me-5-HT 对 5-HT1A、5-HT1B、5-HT1C 和 5-HT2 位点具有低亲和力 (Ki > 500 nM)；该试剂还对 5-HT1D (Ki = 1220 nM) 和 5-HT1E (Ki > 10,000 nM) 位点表现出低亲和力。然而，α-Me-5-HT 对 5-HT1A、5-HT1B、5-HT1C 和 5-HT1D 位点 (Ki 分别 = 42、85、150 和 150 nM) 显示出很小的选择性，并且对 5-HT1E (Ki > 10,000 nM) 位点显示出非常低的亲和力。根据用于标记位点的放射性配体，α-Me-5-HT对5-HT2位点表现出低亲和力（Ki = 880 nM，与[3H]酮色林）或高亲和力（Ki = 3 nM，与[3H]DOB）。这些结果表明，α-Me-5-HT 的选择性不如先前认为的那样，并且在药理学研究中使用该试剂时应谨慎，因为它可能充当混合的 5-HT1/5-HT2 激动剂。
.alpha.-Methyl-5-hydroxytryptamine (.alpha.-Me-5-HT; 2) and 2-methyl-5-hydroxytryptamine (2-Me-5-HT; 3) are considered to be 5-HT2-selective and 5-HT3-selective agents, respectively. These agents were synthesized and examined at serotonin (5-HT) binding sites because there is relatively little documentation as to their selectivity and because they have not been previously examined at the newly discovered 5-HT1D and 5-HT1E sites. As previously reported, 2-Me-5-HT possesses a low affinity (Ki > 500 nM) for 5-HT1A, 5-HT1B, 5-HT1C, and 5-HT2 sites; this agent also displays a low affinity for 5-HT1D (Ki = 1220 nM) and 5-HT1E (Ki > 10,000 nM) sites. However, .alpha.-Me-5-HT displays little selectivity for 5-HT1A, 5-HT1B, 5-HT1C, and 5-HT1D sites (Ki = 42, 85, 150, and 150 nM, respectively) and a very low affinity for 5-HT1E (Ki > 10,000 nM) sites. Depending upon the radioligand used to label the sites, .alpha.-Me-5-HT displays either a low affinity (Ki = 880 nM with [3H]ketanserin) or a high affinity (Ki = 3 nM with [3H]DOB) for 5-HT2 sites. These results suggest that .alpha.-Me-5-HT is not as selective as previously considered and that caution should be used when employing this agent in pharmacological studies because it may act as a mixed 5-HT1/5-HT2 agonist.