Carmo Helena, Remião Fernando, Carvalho Félix, Fernandes Eduarda, de Boer Douwe, dos Reys Lesseps A, de Lourdes Bastos Maria
ICETA/CEQUP, Toxicology Department, Faculty of Pharmacy, University of Porto, Porto, Portugal.
Toxicol Appl Pharmacol. 2003 Aug 1;190(3):262-71. doi: 10.1016/s0041-008x(03)00190-x.
4-Methylthioamphetamine (4-MTA), also known as p-methylthioamphetamine, is a new amphetamine derivative which in humans has been increasingly associated with severe intoxications and several deaths. As hyperthermia is considered to be one of the most life-threatening acute physiological consequences of amphetamine-related intoxications, it was our aim to determine whether 4-MTA induces changes in body temperature in a mouse model. Accordingly, we measured the subcutaneous temperature after acute administration of 4-MTA in CD1 mice. Because hyperthermia seems to result from the central and peripheral actions of catecholamines and serotonin (5-hydroxytriptamine or 5-HT), we also investigated the possible interactions of some catecholaminergic and serotonergic receptor blockers and the inhibition of monoamine oxidase (MAO) with this effect. 4-MTA induced hyperthermia in CD1 mice. Blockade of the 5-HT receptors with methysergide and MAO inhibition with pargyline resulted in the potentiation of the 4-MTA-induced hyperthermic effect. Blockade of the alpha(1)-adrenergic receptors with prazosin completely reverted the 4-MTA-induced hyperthermia while with the beta-adrenergic receptor blocker dl-propranolol this reversal was not complete. Blockade of the alpha(2)-adrenergic receptors with yohimbine had no effect on the hyperthermia induced by 4-MTA. These results suggest that 4-MTA-induced hyperthermia is highly influenced by the catecholaminergic and serotonergic receptor activation and the MAO activity.
4-甲硫基苯丙胺（4-MTA），也被称为对甲硫基苯丙胺，是一种新型苯丙胺衍生物，在人类中，它与严重中毒及多起死亡事件的关联日益增加。由于体温过高被认为是苯丙胺相关中毒最危及生命的急性生理后果之一，我们的目的是确定4-MTA是否会在小鼠模型中引起体温变化。因此，我们测量了CD1小鼠急性给予4-MTA后的皮下温度。由于体温过高似乎是由儿茶酚胺和5-羟色胺（5-羟色胺或5-HT）的中枢和外周作用导致的，我们还研究了一些儿茶酚胺能和5-羟色胺能受体阻滞剂以及单胺氧化酶（MAO）抑制对此效应可能产生的相互作用。4-MTA在CD1小鼠中引起了体温过高。用美西麦角阻断5-HT受体以及用帕吉林抑制MAO会增强4-MTA诱导的体温过高效应。用哌唑嗪阻断α(1)-肾上腺素能受体可完全逆转4-MTA诱导的体温过高，而用β-肾上腺素能受体阻滞剂dl-普萘洛尔时，这种逆转并不完全。用育亨宾阻断α(2)-肾上腺素能受体对4-MTA诱导的体温过高没有影响。这些结果表明，4-MTA诱导的体温过高受到儿茶酚胺能和5-羟色胺能受体激活以及MAO活性的高度影响。
