A review of the influence of functional group modifications to the core scaffold of synthetic cathinones on drug pharmacokinetics

Psychopharmacology (Berl). 2019 Mar;236(3):881-890. doi: 10.1007/s00213-018-4985-6. Epub 2018 Aug 1.

Abstract

Rationale: The synthetic cathinones are a class of designer drugs of abuse that share a common core scaffold. The pharmacokinetic profiles of the synthetic cathinones vary based on the substitutions to the core scaffold.

Objectives: To provide a summary of the literature regarding the pharmacokinetic characteristics of the synthetic cathinones, with a focus on the impact of the structural modifications to the pharmacokinetics.

Results: In many, but not all, instances the pharmacokinetic characteristics of the synthetic cathinones can be reasonably predicted based on the substitutions to the core scaffold. Mephedrone and methylone are chemically alike and have similar Tmax and t1/2 in male rats. MDPV, a structurally distinct synthetic cathinone from mephedrone and methylone, has a lower Tmax and t1/2. Increasing the length of the alkyl chain on the α position of methylone, to produce pentylone, results in increased plasma concentrations and longer t1/2. Metabolism of the synthetic cathinones is reasonably predictable based on the chemical structure, and several phase I metabolites retain pharmacodynamic activity. CYP2D6 is implicated in the metabolism of all of the synthetic cathinones, and other P450s (CYP1A2, CYP2B6, and CYP2C19) are known to contribute variably to the metabolism of specific synthetic cathinones.

Conclusions: Continued research will lead to a better understanding of the pharmacokinetic changes associated with structural modifications to the cathinone scaffold, and potentially in the long range, enhanced overdose and addiction therapy. Additionally, the areas of polydrug use and pharmacogenetics have been largely overlooked with regard to synthetic cathinones.

Keywords: Bath salts; Pharmacokinetics; Review; Synthetic cathinones.

Publication types

  • Review

MeSH terms

  • Alkaloids / adverse effects
  • Alkaloids / chemistry*
  • Alkaloids / pharmacokinetics*
  • Amphetamines / adverse effects
  • Amphetamines / chemistry
  • Amphetamines / pharmacokinetics
  • Animals
  • Designer Drugs / adverse effects
  • Designer Drugs / chemistry
  • Designer Drugs / pharmacokinetics
  • Humans
  • Methamphetamine / adverse effects
  • Methamphetamine / analogs & derivatives
  • Methamphetamine / chemistry
  • Methamphetamine / pharmacokinetics
  • Substance-Related Disorders / epidemiology
  • Substance-Related Disorders / metabolism
  • Synthetic Drugs / adverse effects
  • Synthetic Drugs / chemistry*
  • Synthetic Drugs / pharmacokinetics*

Substances

  • Alkaloids
  • Amphetamines
  • Designer Drugs
  • Synthetic Drugs
  • Methamphetamine
  • cathinone
  • mephedrone
  • pentylone
  • methylone