The AAPS Journal
May 3, 2008
Ai‐ming Yu
60 citations
Indolealkylamine (IAA) drugs, which are serotonin analogs, include both clinically used antimigraine triptans and substances of abuse. Understanding their metabolism and pharmacokinetics helps prevent unwanted drug-drug interactions (DDIs). For abused IAAs like lysergic acid amides, tryptamine derivatives, and beta-carbolines, a stable metabolite can serve as a biomarker for intoxication. Recent studies show that polymorphic cytochrome P450 2D6 (CYP2D6) plays an important role in IAA metabolism, meaning variations in CYP2D6 status can alter metabolism, pharmacokinetics, and toxicity, potentially increasing risk. DDIs with IAAs can also occur at both pharmacokinetic and dynamic levels, possibly leading to severe serotonin toxicity. This review describes the metabolism and potential DDIs of these therapeutic and abused IAA drugs.
Bioanalysis
March 27, 2009
Hong-Wu Shen, Xi-Ling Jiang, Ai‐ming Yu
26 citations
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously measure the psychedelic drug 5-MeO-DMT and its active metabolite bufotenine in mouse serum. Using a simple protein precipitation and 9-minute run, the assay was linear over a wide concentration range with high precision and accuracy. After injecting mice with 2 mg/kg of 5-MeO-DMT, the systemic exposure to bufotenine was about 1/14 that of the parent drug. Because bufotenine binds the 5-HT2A receptor with roughly ten times higher affinity than 5-MeO-DMT, the metabolite may substantially contribute to the drug's overall pharmacological and toxic effects.
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.
The FASEB Journal
April 1, 2012
Ai‐ming Yu
Indolealkylamine drugs like 5-MeO-DMT act on serotonin neurotransmission and are often co-abused with harmaline. Concurrent use of harmaline, a monoamine oxidase inhibitor, blocks the metabolic elimination of 5-MeO-DMT, leading to increased and prolonged exposure. In mice, coadministration of harmaline and 5-MeO-DMT produced more severe hyperthermia than a higher dose of 5-MeO-DMT alone, indicating that harmaline interacts at both pharmacokinetic and pharmacodynamic levels. These results suggest that combining a monoamine oxidase inhibitor with 5-MeO-DMT heightens the risk of serotonin toxicity and intoxication.