Huang X, Marona-Lewicka D, Nichols D E
Department of Pharmacology and Toxicology, Purdue University, School of Pharmacy and Pharmacal Sciences, West Lafayette, IN 47907.
Eur J Pharmacol. 1992 Dec 8;229(1):31-8. doi: 10.1016/0014-2999(92)90282-9.
p-Methylthioamphetamine (MTA), was compared to p-chloroamphetamine (PCA) in a number of pharmacological assays. MTA was about 2-fold more potent than PCA at inhibiting synaptosomal uptake of [3H]5-hydroxytryptamine ([3H]5-HT), and about 7-fold and 10-fold less potent than PCA at inhibiting synaptosomal uptake of [3H]dopamine and [3H]norepinephrine, respectively. In drug discrimination assays, MTA was nearly equipotent to PCA in animals trained to discriminate saline from 3,4-methylenedioxymethamphetamine (MDMA), or two related analogues S-(+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (S-MBDB) or 5-methoxy-6-methyl-2-aminoindan (MMAI). MTA caused dose-dependent increases of tritium efflux from superfused rat frontal cortex slices preloaded with [3H]5-HT, comparable to that induced by an equal molar concentration of PCA. The potential neurotoxicity of MTA was examined by measuring monoamine and metabolite levels at one week following an acute dose. A 10 mg/kg dose of PCA caused a 70-90% decrease of cortical, hippocampal and striatal 5-HT and 5-hydoxyindoleacetic acid (5-HIAA) levels, while twice the molar dose of MTA (21.3 mg/kg) had no effect. Thus, MTA is a potent, selective, serotonin releaser, apparently devoid of serotonin neurotoxic effects. This work also supports the idea that catecholamine systems may play a critical role in the neurotoxicity of PCA-like compounds.
对4-甲硫基苯丙胺（MTA）和4-氯苯丙胺（PCA）进行了多项药理学试验比较。在抑制突触体摄取[3H]5-羟色胺（[3H]5-HT）方面，MTA的效力约为PCA的2倍；而在抑制突触体摄取[3H]多巴胺和[3H]去甲肾上腺素方面，MTA的效力分别比PCA低约7倍和10倍。在药物辨别试验中，对于训练用于区分生理盐水和3,4-亚甲基二氧甲基苯丙胺（MDMA）或两种相关类似物S-(+)-N-甲基-1-(1,3-苯并二氧杂环戊烯-5-基)-2-丁胺（S-MBDB）或5-甲氧基-6-甲基-2-氨基茚（MMAI）的动物，MTA与PCA的效力几乎相当。MTA使预先加载[3H]5-HT的大鼠额叶皮质切片的氚外流呈剂量依赖性增加，与等摩尔浓度的PCA诱导的情况相当。通过在急性给药一周后测量单胺和代谢物水平来研究MTA的潜在神经毒性。10mg/kg剂量的PCA导致皮质、海马和纹状体中5-HT和5-羟吲哚乙酸（5-HIAA）水平降低70-90%，而两倍摩尔剂量的MTA（21.3mg/kg）则没有影响。因此，MTA是一种强效、选择性的5-羟色胺释放剂，显然没有5-羟色胺神经毒性作用。这项研究还支持这样一种观点，即儿茶酚胺系统可能在PCA类化合物的神经毒性中起关键作用。
