Stereochemical effects of 3,4-methylenedioxymethamphetamine (MDMA) and related amphetamine derivatives on inhibition of uptake of [3H]monoamines into synaptosomes from different regions of rat brain.
Stereochemical effects of 3,4-methylenedioxymethamphetamine (MDMA) and related amphetamine derivatives on inhibition of uptake of [3H]monoamines into synaptosomes from different regions of rat brain.
复制标题
3,4-亚甲基二氧基甲基苯丙胺 (MDMA) 和相关苯丙胺衍生物对抑制大鼠脑不同区域突触体摄取 [3H] 单胺的立体化学作用。
DOI：
10.1016/0006-2952(87)90594-6
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发表时间：
1987
影响因子：
5.8
通讯作者：
Yim,GK
中科院分区：
文献类型：
--
作者：
Steele,TD;Nichols,DE;Yim,GK
3，4-亚甲二氧基甲基苯丙胺（MDMA）是一种最近流行的娱乐性药物，尽管有些人认为它具有精神治疗潜力。由于MDMA的药理学在很大程度上尚未确定，因此MDMA及其某些同系物的立体化学特征是通过抑制突触体摄取[3 H]单胺而得出的，并与苯丙胺和致幻性苯异丙胺2，5-二甲氧基-4-甲基苯丙胺（DOM）的立体化学特征进行了比较。与苯丙胺的5倍立体选择性相反，只有MDMA的S-（+）对映体和3，4-亚甲二氧基苯丙胺（MDA）抑制纹状体突触体摄取[3 H]多巴胺。MDMA的α-乙基同系物N-甲基-1-（1，3-苯并二氧杂环戊烯-5-基）-2-丁胺（MBDB）的立体异构体均不抑制[3 H]多巴胺摄取。安非他明和MDMA相关化合物的两种立体异构体在抑制[3 H]去甲肾上腺素摄取到下丘脑突触体中方面是等效的。MDMA的两种立体异构体MDA和MBDB均能有效地抑制海马突触体摄取[~ 3 H]-5-羟色胺，但只有S-（+）-安非他明能明显抑制[~ 3 H]-5-羟色胺的摄取。DOM的两种立体异构体都不能抑制任何[3 H]单胺的突触体摄取。这些结果表明，MDMA及其同系物可能是更密切相关的安非他明，而不是DOM在其生化模式的行动。亚甲二氧基取代的化合物对[3 H]血清素和[3 H]去甲肾上腺素摄取的显著作用暗示这些神经递质参与这些药物的药理作用。
3,4-Methylenedioxymethamphetamine (MDMA) is a recently popularized recreational drug, although some have advocated its psychotherapeutic potential. Since the pharmacology of MDMA is largely uncharacterized, the stereochemical profiles of MDMA and some of its homologs were derived on inhibition of synaptosomal uptake of [3H]monoamines and compared to those of amphetamine and the hallucinogenic phenylisopropylamine 2,5-dimethoxy-4-methylamphetamine (DOM). In contrast to the 5-fold stereoselectivity observed with amphetamine, only theS-(+) enantiomer of MDMA and 3,4-methylenedioxyamphetamine (MDA) inhibited [3H]dopamine uptake into striatal synaptosomes. Neither stereoisomer of the α-ethyl homolog of MDMA,N-methyl-l-(l,3-benzodioxol-5-yl)-2-butanamine (MBDB), inhibited [3H]dopamine uptake. The two stereoisomers of amphetamine and the MDMA-related compounds were equipotent in inhibiting [3H]norepinephrine uptake into hypothalamic synaptosomes. Both steroisomers of MDMA, MDA and MBDB were potent inhibitors of [3H]serotonin uptake into hippocampal synaptosomes, but onlyS-(+)-amphetamine produced an appreciable inhibition of [3H]serotonin uptake. Neither steroisomer of DOM inhibited synaptosomal uptake of any [3H]monoamine. These results suggest that MDMA and its homologs may be more closely related to amphetamine rather than to DOM in their biochemical mode of action. The pronounced effects of the methylenedioxy-substituted compounds on [3H]serotonin and [3H]norepinephrine uptake implicate these neurotransmitters in the pharmacological effects of these drugs.