Absolute configuration and psychotomimetic activity.
Absolute configuration and psychotomimetic activity.
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绝对配置和拟心理活动。
DOI：
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发表时间：
1978
期刊：
影响因子：
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通讯作者：
A. Shulgin
中科院分区：
文献类型：
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作者：
G. Anderson;G. Braun;U. Braun;D. Nichols;A. Shulgin
大多数已知的拟精神病药物在其结构内具有至少一个手性中心，但仅作为外消旋混合物进行了研究。所有以光学活性形式研究的那些都是一致的，因为更有效的异构体是在手性中心具有绝对“R”构型的异构体，其带有对应于苯乙胺部分的氨基的氮。对于 LSD，5“R”、8-“R”异构体在 0.05-0.1 mg 剂量范围内对人体有效，而非对映异构体 1iso-LSD（5-“S”、8-“R”）在 20 倍剂量下对人体无活性（Hofmann 1959）。已经研究了四种环取代的苯基异丙胺拟精神病药的光学活性形式。对于 4 溴-2,5-二甲氧基苯基异丙胺 (DOB)，“R”异构体在 0.5 毫克时有效，大约是外消旋体效力的两倍（Shulgin 等，1971），而“S”异构体的效力仅为约五分之一。据报道，4-甲基-2,5-二甲氧基苯基异丙胺（DOM，STP）的“R”异构体作为拟精神病药的效力比“S”异构体至少强四倍（Shulgin 1973）。 DOB 和 DOM 的这些观察结果与生化研究（Dyer 等人，1973 年）和动物模型（Benington 等人，1973 年）中观察到的结果相似，尽管后者的研究是在接近致死的剂量下进行的。 DOM 的乙基同系物 4 乙基-2,5-二甲氧基苯基异丙胺 (DOET) 已作为其旋光异构体进行了研究（Snyder 等人，1974），此处“R”异构体的活性约为“S”对应异构体的四倍。最后，据报道，3,4-亚甲二氧基苯基异丙胺 (MDA) 的“R”异构体的效力比其旋光对映体强三倍 (Marquardt 1978)。
Most of the known psychotomimetic agents have at least one chiral center within their structures but have been stuaied only as the racemic mixtures. All of those which have been studied in optically active form are consistent in that the more potent isomer is the isomer with the absolute "R" configuration at the chiral center carrying the nitrogen that corresponds to the amino group of the phenethylamine moiety. With LSD, the 5"R",8-"R" isomer is effective in man within the dosage range of 0.05-0.1 mg, whereas the diastereo-isomeric 1iso-LSD (5-"S", 8-"R") is inactive in man at twenty times tnis dosage (Hofmann 1959). Four of the ringsubstituted phenylisopropylamine psychotomimetics have been studied in their optically active forms. With 4bromo-2,5-dimethoxyphenylisopropylamine (DOB) the "R" isomer is effective at 0.5 mg, approximately twice the potency of the racemate (Shulgin et al. 1971), whereas the "S" isomer is only about a fifth as potent. The "R" isomer of 4-methyl-2,5-dimethoxyphenylisopropylamine (DOM, STP) is reported as being at least four times more potent as a psychotomimetic than the "S" isomer (Shulgin 1973). These observations with both DOB and DOM are parallel to those observed in biochemical studies (Dyer et al. 1973) and in animal models (Benington et al. 1973), although these latter studies were conducted at nearly lethal dosages. The ethyl homolog of DOM, 4ethyl-2,5-dimethoxyphenylisopropylamine (DOET), has been studiea as its optical isomers (Snyder et al. 1974) and here again the "R" isomer is approximately four times the activity of the "S" counterpart. Finally, the "R" isomer of 3,4-methylenedioxyphenylisopropylamine (MDA) is reported to be three-fold more potent than its optical enantiomer (Marquardt 1978).