5-HT1 AND 5-HT2 BINDING-PROPERTIES OF DERIVATIVES OF THE HALLUCINOGEN 1-(2,5-DIMETHOXYPHENYL)-2-AMINOPROPANE(2,5-DMA)
5-HT1 AND 5-HT2 BINDING-PROPERTIES OF DERIVATIVES OF THE HALLUCINOGEN 1-(2,5-DIMETHOXYPHENYL)-2-AMINOPROPANE(2,5-DMA)
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DOI：
10.1016/0014-2999(84)90333-9
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发表时间：
1984-01-01
影响因子：
5
通讯作者：
TITELER, M
中科院分区：
文献类型：
--
作者：
SHANNON, M;BATTAGLIA, G;TITELER, M
测定了一系列1-（2.5-二甲氧基苯基）-2-氨基丙烷（2.5-DMA）衍生物和几种相关药物对大鼠皮质5-羟色胺（5-HT）结合位点的亲和力，其中大部分对人具有致幻作用。在竞争试验中，这些药物竞争[3H]酮色林的5-HT2结合，或[3H]LSD的5-HT1结合（在酮色林存在的情况下）。DOI、DOM和DON的R(-)-异构体（即2.5-DMA的4-碘、-甲基和-硝基衍生物）比它们的外消旋物更有效，对5-HT2位点具有选择性。这些相同的因子在竞争[3H]酮色蛋白结合时导致希尔系数显著小于统一；计算机辅助分析表明，双态模型更适合该数据。在10-4 M Gpp(NH)p[5”-鸟酰脲二磷酸]存在时，R(-)- doi的竞争曲线产生接近1的Hill系数。显然，2,5- dma的某些衍生物，特别是R(-)- doi，可能是5-HT2结合位点的有效和选择性激动剂，这些位点可能构成由鸟嘌呤核苷酸调节蛋白调节的5-羟色胺受体。这些药物在5-HT1位点的相互作用具有较低的亲和力和缺乏立体选择性。虽然DOI和DOM是这些致幻剂中最有效的，但就5-羟色胺结合与致幻剂效力之间的可能关系得出任何结论还为时过早。
The affinities of a series of 1-(2.5-dimethoxyphenyl)-2-aminopropane (2.5-DMA) derivatives, most of which are hallucinogenic in man, and several related agents were determined for rat cortical serotonin (5-HT) binding sites. Competition assays were performed in which these agents were competed for the 5-HT2 binding of [3H]ketanserin, or the 5-HT1 binding of [3H]LSD (in the presence of ketanserin). The R(-)-isomers of DOI, DOM and DON (i.e., the 4-iodo, -methyl and -nitro derivatives of 2.5-DMA) were more potent than their racemates and demonstrated selectivity for 5-HT2 sites. These same agents in competing for [3H]ketanserin binding resulted in Hill coefficients significantly less than unity; computer-assisted analysis indicated a 2-state model better fir the data. In the presence of 10-4 M Gpp(NH)p [5''-guanylimidodiphosphate] the competition curve for R(-)-DOI produced a Hill coefficient close to unity. Apparently, certain derivatives of 2,5-DMA, in particular R(-)-DOI, may be potent and selective agonists at 5-HT2 binding sites, sites that may constitute a serotonin receptor regulated by a guanine nucleotide regulatory protein. The interactions of these agents at 5-HT1 sites was with a lower affinity and a lack of stereoselectivity. Although DOI and DOM are among the most potent of these agents as hallucinogens, it is still too premature to draw any conclusions regarding a possible relationship between 5-HT binding and hallucinogenic potency.