Details
- Autor(en) / Beteiligte
- Titel
- Evaluating kratom alkaloids using PHASE
- Ist Teil von
- PloS one, 2020-03, Vol.15 (3), p.e0229646
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Kratom is a botanical substance that is marketed and promoted in the US for pharmaceutical opioid indications despite having no US Food and Drug Administration approved uses. Kratom contains over forty alkaloids including two partial agonists at the mu opioid receptor, mitragynine and 7-hydroxymitragynine, that have been subjected to the FDA's scientific and medical evaluation. However, pharmacological and toxicological data for the remaining alkaloids are limited. Therefore, we applied the Public Health Assessment via Structural Evaluation (PHASE) protocol to generate in silico binding profiles for 25 kratom alkaloids to facilitate the risk evaluation of kratom. PHASE demonstrates that kratom alkaloids share structural features with controlled opioids, indicates that several alkaloids bind to the opioid, adrenergic, and serotonin receptors, and suggests that mitragynine and 7-hydroxymitragynine are the strongest binders at the mu opioid receptor. Subsequently, the in silico binding profiles of a subset of the alkaloids were experimentally verified at the opioid, adrenergic, and serotonin receptors using radioligand binding assays. The verified binding profiles demonstrate the ability of PHASE to identify potential safety signals and provide a tool for prioritizing experimental evaluation of high-risk compounds.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0229646Titel-ID: cdi_doaj_primary_oai_doaj_org_article_a24feac975674604922bfa76f58965bb
- Format
- –
- Schlagworte
- 60 APPLIED LIFE SCIENCES, adrenergic signal transduction, Alkaloids, Animals, Binding Sites, Biology and Life Sciences, computer software, Drug approval, HEK293 Cells, Humans, In Vitro Techniques, Kratom, Marketing, Medicine and Health Sciences, Mitragyna - chemistry, molecular docking, Molecular Docking Simulation, Opioids, Phenols (Class of compounds), Physical Sciences, Plants, Medicinal - chemistry, Public health, Public health movements, Radioligand Assay, receptor binding assays, Receptors, Adrenergic - drug effects, Receptors, Adrenergic - metabolism, Receptors, Opioid - drug effects, Receptors, Opioid - metabolism, Receptors, Opioid, mu - drug effects, Receptors, Opioid, mu - metabolism, Receptors, Serotonin - drug effects, Receptors, Serotonin - metabolism, Research and Analysis Methods, Risk assessment, Secologanin Tryptamine Alkaloids - chemistry, Secologanin Tryptamine Alkaloids - pharmacokinetics, Secologanin Tryptamine Alkaloids - pharmacology, serotonin, serotonin receptors, Structure-Activity Relationship