Evaluating kratom alkaloids using PHASE

• DOI: 10.1371/journal.pone.0229646
• Publication Date: 2020-03-03T14:02:31Z
• Authors: Christopher R. Ellis; Rebecca Racz; Naomi L. Kruhlak; Marlene T. Kim; Alexey V. Zakharov; Noel Southall; Edward G. Hawkins; Keith Burkhart; David G. Strauss; Lidiya Stavitskaya
• Keywords: 0301 basic medicine; Binding Sites; Plants, Medicinal; Mitragyna; Science; Q; R; Receptors, Opioid, mu; In Vitro Techniques; Secologanin Tryptamine Alkaloids; Receptors, Adrenergic; 3. Good health; Molecular Docking Simulation; Radioligand Assay; Structure-Activity Relationship; 03 medical and health sciences; HEK293 Cells; Receptors, Serotonin; Receptors, Opioid; Medicine; Animals; Humans; Research Article

Kratom is a botanical substance that marketed and promoted in the US for pharmaceutical opioid indications despite having no Food Drug Administration approved uses. contains over forty alkaloids including two partial agonists at mu receptor, mitragynine 7-hydroxymitragynine, have been subjected to FDA's scientific medical evaluation. However, pharmacological toxicological data remaining are limited. Therefore, we applied Public Health Assessment via Structural Evaluation (PHASE) protocol generate silico binding profiles 25 kratom facilitate risk evaluation of kratom. PHASE demonstrates share structural features with controlled opioids, indicates several bind opioid, adrenergic, serotonin receptors, suggests 7-hydroxymitragynine strongest binders receptor. Subsequently, subset were experimentally verified receptors using radioligand assays. The demonstrate ability identify potential safety signals provide tool prioritizing experimental high-risk compounds.