Johnson M, Letter A A, Merchant K, Hanson G R, Gibb J W
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112.
J Pharmacol Exp Ther. 1988 Mar;244(3):977-82.
This study demonstrates that the isomers of 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) are different in their ability to induce changes in serotonergic parameters and nigral concentrations of neurotensin-like immunoreactivity. With five successive doses (3.5 mg/kg) the d-MDA isomer was more potent than the l-MDA in its ability to decrease the concentrations of serotonin in the frontal cortex and hippocampus. The same difference occurred in the ability to decrease the hippocampal activity of tryptophan hydroxylase as well as the hippocampal and neostriatal 5-hydroxyindoleacetic acid concentrations. However, both isomers of MDMA were equipotent in their ability to decrease serotonergic parameters in the brain areas examined. When the doses were increased to 5 and 10 mg/kg, both isomers of MDA were equipotent in their effects on the serotonin system, whereas the l-MDMA was significantly less potent than its d isomeric counterpart in causing a decrease in serotonergic parameters of the different brain areas. In contrast, treatments with any of the isomers appeared to have a minimal impact on neostriatal dopaminergic parameters. However, treatment with MDA or MDMA caused increases in the nigral concentrations of neurotensin, with the d isomer of both compounds having substantially greater effects on this neuropeptide system. These increases are suspected to result from drug-released dopamine. This study demonstrates that at selected doses, the d isomers of MDA and MDMA are more potent than their l forms in affecting neurochemical systems, whereas high doses of either isomer of MDA share a common ability to induce changes in the serotonergic system that are likely associated with neuronal damage.
本研究表明，3,4-亚甲基二氧基苯丙胺（MDA）和3,4-亚甲基二氧基甲基苯丙胺（MDMA）的异构体在诱导血清素能参数变化以及黑质中神经降压素样免疫反应性浓度变化的能力方面存在差异。连续给予五次剂量（3.5毫克/千克）时，d-MDA异构体在降低额叶皮质和海马体中血清素浓度的能力上比l-MDA更强。在降低色氨酸羟化酶的海马体活性以及海马体和新纹状体中5-羟吲哚乙酸浓度的能力方面也出现了同样的差异。然而，MDMA的两种异构体在降低所检查脑区的血清素能参数的能力上是等效的。当剂量增加到5毫克/千克和10毫克/千克时，MDA的两种异构体对血清素系统的作用是等效的，而l-MDMA在导致不同脑区血清素能参数降低方面明显不如其d异构体有效。相比之下，用任何一种异构体进行处理似乎对新纹状体多巴胺能参数的影响最小。然而，用MDA或MDMA进行处理会导致黑质中神经降压素浓度升高，这两种化合物的d异构体对该神经肽系统的影响要大得多。这些升高被怀疑是由药物释放的多巴胺引起的。本研究表明，在选定的剂量下，MDA和MDMA的d异构体在影响神经化学系统方面比其l形式更有效，而高剂量的MDA的任何一种异构体都具有诱导血清素能系统变化的共同能力，这种变化可能与神经元损伤有关。
