Evaluating kratom alkaloids using PHASE
| Autor: | Rebecca Racz, Marlene T. Kim, Lidiya Stavitskaya, Alexey V. Zakharov, David G. Strauss, Christopher R. Ellis, Naomi L. Kruhlak, Noel Southall, Keith Burkhart, Edward G. Hawkins |
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| Rok vydání: | 2019 |
| Předmět: |
Receptors
Opioid mu Pharmacology Biochemistry chemistry.chemical_compound Radioligand Assay Binding Analysis 0302 clinical medicine Computational Chemistry Medicine and Health Sciences heterocyclic compounds Receptor 0303 health sciences Analgesics Multidisciplinary Drugs Neurochemistry Neurotransmitters 3. Good health Receptors Adrenergic Molecular Docking Molecular Docking Simulation Chemistry Physical Sciences Medicine μ-opioid receptor medicine.drug Research Article Signal Transduction Biogenic Amines Serotonin Transmembrane Receptors Science In silico In Vitro Techniques Research and Analysis Methods Partial agonist 03 medical and health sciences Structure-Activity Relationship Alkaloids medicine Animals Humans Pain Management Receptor Binding Assays 5-HT receptor Chemical Characterization 030304 developmental biology Binding Sites Plants Medicinal Mitragyna Chemical Compounds Biology and Life Sciences Proteins Cell Biology Secologanin Tryptamine Alkaloids Opioids HEK293 Cells chemistry Opioid Mitragynine Receptors Serotonin Receptors Opioid 030217 neurology & neurosurgery Serotonin Receptors Neuroscience Adrenergic Signal Transduction |
| Zdroj: | PLoS ONE PLoS ONE, Vol 15, Iss 3, p e0229646 (2020) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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