Johnson M, Elayan I, Hanson G R, Foltz R L, Gibb J W, Lim H K
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City.
J Pharmacol Exp Ther. 1992 May;261(2):447-53.
The effects of 3,4-dihydroxymethamphetamine (DHM) and 2,4,5-trihydroxymethamphetamine (THM) on central serotonergic and dopaminergic systems were investigated to determine if these metabolites share the neurochemical properties of 3,4-methylenedioxymethamphetamine. THM (50-200 micrograms) or DHM (135 micrograms) was administered i.c.v. to rats; 5 days later, cortical, striatal and hippocampal tryptophan hydroxylase (TPH) activity were decreased by THM in a dose-dependent manner, whereas DHM was without effect in these brain structures. The concentration of serotonin in the brain structures contralateral to the side of THM injection was also decreased, but to a lesser degree. THM (100 and 200 micrograms) increased TPH activity to 155% of control in the dorsal raphe, whereas a dose of 50 micrograms increased TPH activity to 132% of control in the median raphe nucleus. THM also markedly reduced striatal tyrosine hydroxylase activity, but did not alter enzyme activity in the substantia nigra; DHM increased striatal tyrosine hydroxylase activity to 115% of control. These results suggest that THM, but not DHM, is toxic to both dopaminergic and serotonergic nerve terminals. Although THM could not be established as the neurotoxic metabolite explaining 3,4-methylenedioxymethamphetamine (MDMA) toxicity, its properties may prove useful in elucidating amphetamine toxicity.
研究了3,4 - 二羟基甲基苯丙胺（DHM）和2,4,5 - 三羟基甲基苯丙胺（THM）对中枢5 - 羟色胺能和多巴胺能系统的影响，以确定这些代谢产物是否具有3,4 - 亚甲基二氧基甲基苯丙胺的神经化学特性。将THM（50 - 200微克）或DHM（135微克）经脑室内注射给大鼠；5天后，THM以剂量依赖的方式降低了皮质、纹状体和海马体中色氨酸羟化酶（TPH）的活性，而DHM对这些脑结构没有影响。在THM注射侧对侧的脑结构中5 - 羟色胺的浓度也降低了，但程度较小。THM（100和200微克）使背侧中缝核中的TPH活性增加至对照的155%，而50微克的剂量使中缝正中核中的TPH活性增加至对照的132%。THM还显著降低了纹状体酪氨酸羟化酶的活性，但未改变黑质中的酶活性；DHM使纹状体酪氨酸羟化酶活性增加至对照的115%。这些结果表明，THM而非DHM对多巴胺能和5 - 羟色胺能神经末梢均有毒性。尽管THM不能被确定为解释3,4 - 亚甲基二氧基甲基苯丙胺（摇头丸）毒性的神经毒性代谢产物，但其特性可能有助于阐明苯丙胺类药物的毒性。
