Comparative neuropharmacology of three psychostimulant cathinone derivatives: butylone, mephedrone and methylone

Br J Pharmacol. 2012 Sep;167(2):407-20. doi: 10.1111/j.1476-5381.2012.01998.x.


Background and purpose: Here, we have compared the neurochemical profile of three new cathinones, butylone, mephedrone and methylone, in terms of their potential to inhibit plasmalemmal and vesicular monoamine transporters. Their interaction with 5-HT and dopamine receptors and their psychostimulant effect was also studied.

Experimental approach: Locomotor activity was recorded in mice following different doses of cathinones. Monoamine uptake assays were performed in purified rat synaptosomes. Radioligand-binding assays were carried out to assess the affinity of these compounds for monoamine transporters or receptors.

Key results: Butylone, mephedrone and methylone (5-25 mg·kg(-1) ) caused hyperlocomotion, which was prevented with ketanserin or haloperidol. Methylone was the most potent compound inhibiting both [(3) H]5-HT and [(3) H]dopamine uptake with IC(50) values that correlate with its affinity for dopamine and 5-HT transporter. Mephedrone was found to be the cathinone derivative with highest affinity for vesicular monoamine transporter-2 causing the inhibition of dopamine uptake. The affinity of cathinones for 5-HT(2A) receptors was similar to that of MDMA.

Conclusions and implications: Butylone and methylone induced hyperlocomotion through activating 5-HT(2A) receptors and increasing extra-cellular dopamine. They inhibited 5-HT and dopamine uptake by competing with substrate. Methylone was the most potent 5-HT and dopamine uptake inhibitor and its effect partly persisted after withdrawal. Mephedrone-induced hyperlocomotion was dependent on endogenous 5-HT. Vesicular content played a key role in the effect of mephedrone, especially for 5-HT uptake inhibition. The potency of mephedrone in inhibiting noradrenaline uptake suggests a sympathetic effect of this cathinone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Methylenedioxyamphetamine / analogs & derivatives*
  • 3,4-Methylenedioxyamphetamine / chemistry
  • 3,4-Methylenedioxyamphetamine / pharmacology
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Carrier Proteins
  • Central Nervous System Stimulants / chemistry
  • Central Nervous System Stimulants / pharmacology
  • Dopamine / metabolism
  • Dopamine Antagonists / pharmacology
  • Dose-Response Relationship, Drug
  • Haloperidol / pharmacology
  • Ketanserin / pharmacology
  • Male
  • Methamphetamine / analogs & derivatives*
  • Methamphetamine / chemistry
  • Methamphetamine / pharmacokinetics
  • Methamphetamine / pharmacology
  • Mice
  • Molecular Structure
  • Motor Activity / drug effects*
  • Norepinephrine / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism
  • Serotonin Antagonists / pharmacology
  • Synaptosomes / drug effects


  • Carrier Proteins
  • Central Nervous System Stimulants
  • Dopamine Antagonists
  • Serotonin Antagonists
  • Serotonin
  • Methamphetamine
  • 3,4-Methylenedioxyamphetamine
  • mephedrone
  • Ketanserin
  • Haloperidol
  • methylone
  • Dopamine
  • Norepinephrine
  • 2-methylamino-1-(3,4-methylenedioxyphenyl)butan-1-one