Mephedrone and Its Metabolites: A Narrative Review

TL;DR

This review explores mephedrone's structure, metabolism, and toxic effects, focusing on its metabolites for detection and forensic use.

Contribution

The paper provides a detailed analysis of mephedrone's metabolic pathways and enantiomeric properties for forensic and toxicological applications.

Findings

Mephedrone has two enantiomeric forms with different pharmacological profiles.

Phase I and II metabolites like normephedrone and N-succinyl-normephedrone are identified as potential biomarkers.

Metabolism influences mephedrone's neurochemical effects and toxicological risks.

Abstract

New psychoactive substances (NPSs) have emerged as a significant global public health challenge due to their ability to mimic traditional drugs. Among these, mephedrone has gained attention because of its widespread use and associated toxicities. This review provides a comprehensive analysis of the structure, pharmacokinetic properties, and metabolic pathways of mephedrone, highlighting its phase I and phase II metabolites as potential biomarkers for detection and forensic applications. A comprehensive literature search was performed without date restrictions. The search employed key terms such as “mephedrone metabolites”, “pharmacokinetics of mephedrone”, “phase I metabolites of mephedrone”, and “phase II metabolites of mephedrone”. Additionally, the reference lists of selected studies were screened to ensure a thorough review of the literature. Mephedrone is a chiral compound existing in two enantiomeric forms, exhibiting different affinities for monoamine transporters and distinct pharmacological profiles. In vivo animal studies indicate rapid absorption, significant tissue distribution, and the formation of multiple phase I metabolites (e.g., normephedrone, dihydromephedrone, 4-carboxymephedrone) that influence its neurochemical effects. Phase II metabolism involves conjugation reactions leading to metabolites such as N-succinyl-normephedrone and N-glutaryl-normephedrone, further complicating its metabolic profile. These findings underscore the importance of elucidating mephedrone’s metabolic pathways to improve detection methods, enhance our understanding of its toxicological risks, and inform future therapeutic strategies.

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