Indolealkylamines: biotransformations and potential drug-drug interactions.
Indolealkylamine (IAA) drugs are 5-hydroxytryptamine (5-HT or serotonin) analogs that mainly act on the serotonin system. Some IAAs are clinically utilized for antimigraine therapy, whereas other substances are notable as drugs of abuse. In the clinical evaluation of antimigraine triptan drugs, studies on their biotransformations and pharmacokinetics would facilitate the understanding and prevention of unwanted drug-drug interactions (DDIs). A stable, principal metabolite of an IAA drug of abuse could serve as a useful biomarker in assessing intoxication of the IAA substance. Studies on the metabolism of IAA drugs of abuse including lysergic acid amides, tryptamine derivatives and beta-carbolines are therefore emerging. An important role for polymorphic cytochrome P450 2D6 (CYP2D6) in the metabolism of IAA drugs of abuse has been revealed by recent studies, suggesting that variations in IAA metabolism, pharmaco- or toxicokinetics and dynamics can arise from distinct CYP2D6 status, and CYP2D6 polymorphism may represent an additional risk factor in the use of these IAA drugs. Furthermore, DDIs with IAA agents could occur additively at the pharmaco/toxicokinetic and dynamic levels, leading to severe or even fatal serotonin toxicity. In this review, the metabolism and potential DDIs of these therapeutic and abused IAA drugs are described.
Yu
Ai-Ming
AM
Department of Pharmaceutical Sciences, University at Buffalo, The State University of New York, 541 Cooke Hall, Buffalo, New York, 14260-1200, USA. aimingyu@buffalo.edu
D000818:Animals; D001711:Biotransformation; D004347:Drug Interactions; D006801:Humans; D013287:Illicit Drugs / Q000009:adverse effects / Q000493:pharmacokinetics; D008881:Migraine Disorders / Q000188:drug therapy; D015394:Molecular Structure; D012701:Serotonin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D018490:Serotonin Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
D013287:Illicit Drugs; D018490:Serotonin Agents; D012701:Serotonin