AUTHOR=Don Charleen G. , Smieško Martin TITLE=In Silico Pharmacogenetics CYP2D6 Study Focused on the Pharmacovigilance of Herbal Antidepressants JOURNAL=Frontiers in Pharmacology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.00683 DOI=10.3389/fphar.2020.00683 ISSN=1663-9812 ABSTRACT=

The annual increase in depression worldwide together with an upward trend in the use of alternative medicine as treatment asks for developing reliable safety profiles of herbal based medicine. A considerable risk on adverse reactions exists when herbal remedies are combined with prescription medication. Around 25% of the drugs, including many antidepressants, depend on the activity of CYP2D6 for their metabolism and corresponding efficacy. Therefore, probing CYP2D6 inhibition by the active substances in herbal based medicine within the wild-type enzyme and clinically relevant allelic variants is crucial to avoid toxicity issues. In this in silico study several compounds with herbal origin suggested to have antidepressant activity were analyzed on their CYP2D6 wild-type and CYP2D6*53 inhibition potential using molecular docking. In addition, several pharmacokinetic properties were evaluated to assess their probability to cross the blood brain barrier and subsequently reach sufficient brain bioavailability for the modulation of central nervous system targets as well as characteristics which may hint toward potential safety issues.