Development of a mechanism-based pharmacokinetic/pharmacodynamic model to characterize the thermoregulatory effects of serotonergic drugs in mice
Acta Pharmaceutica Sinica B August 6, 2016 Xi-Ling Jiang, Hong-Wu Shen, Donald E. Mager et al. 4 citations
A new computer model describes how the drug harmaline, which inhibits the enzyme monoamine oxidase A, alters body temperature in mice when combined with the serotonin receptor agonist 5-MeO-DMT. Harmaline causes hypothermia by activating 5-HT1A receptors, while 5-MeO-DMT triggers hyperthermia by stimulating 5-HT2A receptors. The model successfully separates drug-induced fever from stress-induced fever caused by handling and injection. When harmaline is given alongside 5-MeO-DMT, the concentration of 5-MeO-DMT needed to produce hyperthermia drops fourfold, showing a quantitative interaction. Dangerous overheating from toxic doses is linked to increased harmaline exposure, not 5-MeO-DMT. This framework may help predict how serotonergic drugs and stress affect thermoregulation.