4-Methylthioamphetamine-induced hyperthermia in mice: influence of serotonergic and catecholaminergic pathways

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology
  • Amphetamines / toxicity*
  • Animals
  • Body Temperature / drug effects*
  • Body Temperature / physiology
  • Catecholamines / physiology*
  • Hyperthermia, Induced*
  • Male
  • Methysergide / pharmacology
  • Mice
  • Mice, Inbred Strains
  • Monoamine Oxidase / metabolism
  • Monoamine Oxidase Inhibitors / pharmacology
  • Pargyline / pharmacology
  • Prazosin / pharmacology
  • Receptors, Adrenergic / metabolism
  • Receptors, Serotonin / metabolism
  • Serotonin / physiology*
  • Serotonin Antagonists / pharmacology


  • Adrenergic alpha-Antagonists
  • Amphetamines
  • Catecholamines
  • Monoamine Oxidase Inhibitors
  • Receptors, Adrenergic
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin
  • 4-methylthioamphetamine
  • Pargyline
  • Monoamine Oxidase
  • Prazosin
  • Methysergide