4-Bromo-2,5-dimethoxyphenethylamine (2C-B) and structurally related phenylethylamines are potent 5-HT2A receptor antagonists in Xenopus laevis oocytes
4-Bromo-2,5-dimethoxyphenethylamine (2C-B) and structurally related phenylethylamines are potent 5-HT2A receptor antagonists in Xenopus laevis oocytes
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DOI：
10.1038/sj.bjp.0705722
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发表时间：
2004-04-01
影响因子：
7.3
通讯作者：
Huidobro-Toro, JP
中科院分区：
文献类型：
--
作者：
Villalobos, CA;Bull, P;Huidobro-Toro, JP
1我们最近报道了几种2-（2,5-二甲氧基-4-取代苯基）乙胺（PEAs），包括4-I = 2C-I、4-Br = 2C-B和4-CH3 = 2C-D类似物，它们是5-HT2C受体的部分激动剂，对5-HT2A受体的内在功效很低甚至可以忽略不计。这些结果提出了这些药物可能作为5-HT2拮抗剂的建议为了验证这一假设，将非洲爪蟾卵母细胞与5-HT2A或5-HT2C受体的大鼠克隆显微注射。上述豌豆及其4-H类似物（2C-H）阻断5- ht诱导的5-HT2A电流，但不阻断5-HT2C受体，显示5-HT2受体亚型选择性。5-HT2A受体拮抗剂需要2分钟的预孵育才能达到最大的抑制作用所有被试豌豆的5-HT浓度响应曲线都向右和向下移动。它们的效力随C(4)取代基的性质而变化；其5-HT2A受体拮抗剂效价的相对等级为2C-I>2C-B>2C-D>2C-H.4目前的研究结果表明，在蛋鸡卵母细胞中，一系列2,5-二甲氧基-4取代的豌豆阻断了5-HT2A而不是5-HT2C受体介导的反应。作为另一种假设，我们认为豌豆的精神兴奋活性可能并不完全与部分或完全5-HT2A受体激动作用相关。
1 We recently described that several 2-(2,5-dimethoxy-4-substituted phenyl) ethylamines (PEAs), including 4-I = 2C-I, 4-Br = 2C-B, and 4-CH3 = 2C-D analogs, are partial agonists at 5-HT2C receptors, and show low or even negligible intrinsic efficacy at 5-HT2A receptors. These results raised the proposal that these drugs may act as 5-HT2 antagonists.2 To test this hypothesis, Xenopus laevis oocytes were microinjected with the rat clones for 5-HT2A or 5-HT2C receptors. The above-mentioned PEAs and its 4-H analog (2C-H) blocked the 5-HT-induced currents at 5-HT2A, but not at the 5-HT2C receptor, revealing 5-HT2 receptor subtype selectivity. The 5-HT2A receptor antagonism required a 2-min preincubation to attain maximum inhibition.3 All PEAs tested shifted the 5-HT concentration-response curves to the right and downward. Their potencies varied with the nature of the C(4) substituent; the relative rank order of their 5-HT2A receptor antagonist potency was 2C-I>2C-B>2C-D>2C-H.4 The present results demonstrate that in X. laevis oocytes, a series of 2,5-dimethoxy-4-substituted PEAs blocked the 5-HT2A but not the 5-HT2C receptor-mediated responses. As an alternative hypothesis, we suggest that the psychostimulant activity of the PEAs may not be exclusively associated with partial or full 5-HT2A receptor agonism.