EFFECTS OF CERTAIN HALLUCINOGENIC AMPHETAMINE ANALOGS ON THE RELEASE OF [H-3]-LABELED SEROTONIN FROM RAT-BRAIN SYNAPTOSOMES
EFFECTS OF CERTAIN HALLUCINOGENIC AMPHETAMINE ANALOGS ON THE RELEASE OF [H-3]-LABELED SEROTONIN FROM RAT-BRAIN SYNAPTOSOMES
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DOI：
10.1021/jm00347a010
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发表时间：
1982-01-01
影响因子：
7.3
通讯作者：
YIM, GKW
中科院分区：
文献类型：
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作者：
NICHOLS, DE;LLOYD, DH;YIM, GKW
对3,4 -（亚甲二氧基）安非他明（MDA）、对甲氧基安非他明（PMA）和N-Me-MDA （MDMA）的对映体及其二甲基化衍生物进行了评估，以评估其对大鼠全脑突触体释放[3H]血清素的影响。安非他明同分异构体在浓度为1和10µ时均能诱导[3H]血清素的释放，但在浓度为0.1µ时则无活性。在10µ浓度下，异构体的效力无显著差异。然而，在1µ时，mdma的（+）异构体比（-）异构体更有效地诱导释放。由于临床上具有活性的是（+）异构体，这一结果提示递质释放可能在MDMA的生物活性中起作用。相比之下，即使在最高的沐浴浓度下，a，«-二甲基化合物也不能有效地释放血清素。致幻苯乙胺衍生物通过立体选择过程产生中枢效应。在已研究的情况下，药理学作用是由具有R绝对构型的异构体选择性地引起的。除了3,4 -（亚甲二氧基）安非他胺（MDA, 1）外，甲基化显著地减弱或消除了这一系列的活性。在MDA的情况下，一个奇怪的逆转
The enantiomers of 3, 4-(methylenedioxy) amphetamine (MDA), p-methoxyamphetamine (PMA), and N-Me-MDA (MDMA), along with their,-dimethylated derivatives, were evaluated for an effect on the release of [3H] serotonin from rat whole brain synaptosomes. The amphetamine isomers were all potent in inducing the release of [3H] serotonin at bath concentrations of 1 and 10 µ but were inactive at 0.1 µ. No significant difference in isomer potency was observed at the 10-µ concentration. However, at 1 µ the (+) isomer ofMDMA was more effective in inducing release than was the (-) isomer. Since it is the (+) isomer which is clinically active, this result suggests that transmitter release may play a role in the biological activity of MDMA. By contrast, the a,«-dimethyl compounds were not effective in releasing serotonin, even at the highest bath concentration.Hallucinogenic phenethylamine derivatives produce their central effects through a stereoselective process. In those cases which have been examined, the pharmacological effects are selectively elicited by the isomer possessing the R absolute configuration. 1" 6 7N-Methylation consid-erably attenuates or abolishes activity in this series, with the notable exception of 3, 4-(methylenedioxy) amphet-amine (MDA, l). 7 In the case of MDA a curious reversal