In silico investigation of mitragynine and 7-hydroxymitragynine metabolism

Mitragynine is the main active compound of Mitragyna speciose (Kratom in Thai). The understanding of mitragynine derivative metabolism in human body is required to develop effective detection techniques in case of drug abuse or establish an appropriate dosage in case of medicinal uses. This in silic...

Full description

Saved in:

Bibliographic Details
Published in:	BMC research notes 2019-07, Vol.12 (1), p.451-451, Article 451
Main Authors:	Limpanuparb, Taweetham, Noorat, Rattha, Tantirungrotechai, Yuthana
Format:	Article
Language:	eng
Subjects:	7-Hydroxymitragynine Analysis Animals Chemical properties Computer Simulation Demethylation Density functional theory Density functionals Drug abuse Glucuronic Acid - chemistry Glucuronic Acid - metabolism Health aspects Humans Investigations Kratom Metabolic Networks and Pathways Metabolism Metabolites Mitragyna - chemistry Mitragynine Models, Chemical Molecular Structure Plant metabolites Rats Research Note Secologanin Tryptamine Alkaloids - analysis Secologanin Tryptamine Alkaloids - chemistry Secologanin Tryptamine Alkaloids - metabolism Substance Abuse Detection - methods Substance-Related Disorders - diagnosis Substance-Related Disorders - metabolism Substance-Related Disorders - prevention & control Testing
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Mitragynine is the main active compound of Mitragyna speciose (Kratom in Thai). The understanding of mitragynine derivative metabolism in human body is required to develop effective detection techniques in case of drug abuse or establish an appropriate dosage in case of medicinal uses. This in silico study is based upon in vivo results in rat and human by Philipp et al. (J Mass Spectrom 44:1249-1261, 2009). Gas-phase structures of mitragynine, 7-hydroxymitragynine and their metabolites were obtained by quantum chemical method at B3LYP/6-311++G(d,p) level. Results in terms of standard Gibbs energies of reaction for all metabolic pathways are reported with solvation energy from SMD model. We found that 7-hydroxy substitution leads to changes in reactivity in comparison to mitragynine: position 17 is more reactive towards demethylation and conjugation with glucuronic acid and position 9 is less reactive towards conjugation with glucuronic acid. Despite the changes, position 9 is the most reactive for demethylation and position 17 is the most reactive for conjugation with glucuronic acid for both mitragynine and 7-hydroxymitragynine. Our results suggest that 7-hydroxy substitution could lead to different metabolic pathways and raise an important question for further experimental studies of this more potent derivative.
ISSN:	1756-0500 1756-0500