In silico investigation of mitragynine and 7-hydroxymitragynine metabolism

Abstract

Objective 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 ). Results 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. Electronic supplementary material The online version of this article (10.1186/s13104-019-4461-3) contains supplementary material, which is available to authorized users.

An in silico investigation of menthol metabolism

“…The solvation energies in water of the gas-phase structures were calculated with the SMD model [22] through single-point energy calculations. The calculation of Gibbs energies in solution phase is the same as in our previous work [23, 24] where there is a correction for the standard state of liquid water (~ 55 mol/L) [25–28]. All quantum chemical calculations were performed using the Q-Chem 5.1 program package [29].…”

“…All quantum chemical calculations were performed using the Q-Chem 5.1 program package [29]. (Shell script, spreadsheet templates, and Mathematica [30] notebook used were modified from our previous work [23, 24]. All output files and other associated codes to obtain the standard Gibbs energies of the reaction are provided in S2 File and S3 File, respectively.)…”