Tags

Type your tag names separated by a space and hit enter

The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue.
Neuropsychopharmacology. 2012 Apr; 37(5):1192-203.N

Abstract

The nonmedical use of 'designer' cathinone analogs, such as 4-methylmethcathinone (mephedrone) and 3,4-methylenedioxymethcathinone (methylone), is increasing worldwide, yet little information is available regarding the mechanism of action for these drugs. Here, we employed in vitro and in vivo methods to compare neurobiological effects of mephedrone and methylone with those produced by the structurally related compounds, 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine. In vitro release assays using rat brain synaptosomes revealed that mephedrone and methylone are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity. In vivo microdialysis in rat nucleus accumbens showed that i.v. administration of 0.3 and 1.0 mg/kg of mephedrone or methylone produces dose-related increases in extracellular dopamine and serotonin (5-HT), with the magnitude of effect on 5-HT being greater. Both methcathinone analogs were weak motor stimulants when compared with methamphetamine. Repeated administrations of mephedrone or methylone (3.0 and 10.0 mg/kg, s.c., 3 doses) caused hyperthermia but no long-term change in cortical or striatal amines, whereas similar treatment with MDMA (2.5 and 7.5 mg/kg, s.c., 3 doses) evoked robust hyperthermia and persistent depletion of cortical and striatal 5-HT. Our data demonstrate that designer methcathinone analogs are substrates for monoamine transporters, with a profile of transmitter-releasing activity comparable to MDMA. Dopaminergic effects of mephedrone and methylone may contribute to their addictive potential, but this hypothesis awaits confirmation. Given the widespread use of mephedrone and methylone, determining the consequences of repeated drug exposure warrants further study.

Authors+Show Affiliations

Translational Pharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. mbaumann@mail.nih.govNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22169943

Citation

Baumann, Michael H., et al. "The Designer Methcathinone Analogs, Mephedrone and Methylone, Are Substrates for Monoamine Transporters in Brain Tissue." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 37, no. 5, 2012, pp. 1192-203.
Baumann MH, Ayestas MA, Partilla JS, et al. The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsychopharmacology. 2012;37(5):1192-203.
Baumann, M. H., Ayestas, M. A., Partilla, J. S., Sink, J. R., Shulgin, A. T., Daley, P. F., Brandt, S. D., Rothman, R. B., Ruoho, A. E., & Cozzi, N. V. (2012). The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 37(5), 1192-203. https://doi.org/10.1038/npp.2011.304
Baumann MH, et al. The Designer Methcathinone Analogs, Mephedrone and Methylone, Are Substrates for Monoamine Transporters in Brain Tissue. Neuropsychopharmacology. 2012;37(5):1192-203. PubMed PMID: 22169943.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue. AU - Baumann,Michael H, AU - Ayestas,Mario A,Jr AU - Partilla,John S, AU - Sink,Jacqueline R, AU - Shulgin,Alexander T, AU - Daley,Paul F, AU - Brandt,Simon D, AU - Rothman,Richard B, AU - Ruoho,Arnold E, AU - Cozzi,Nicholas V, Y1 - 2011/12/14/ PY - 2011/12/16/entrez PY - 2011/12/16/pubmed PY - 2012/7/21/medline SP - 1192 EP - 203 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 37 IS - 5 N2 - The nonmedical use of 'designer' cathinone analogs, such as 4-methylmethcathinone (mephedrone) and 3,4-methylenedioxymethcathinone (methylone), is increasing worldwide, yet little information is available regarding the mechanism of action for these drugs. Here, we employed in vitro and in vivo methods to compare neurobiological effects of mephedrone and methylone with those produced by the structurally related compounds, 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine. In vitro release assays using rat brain synaptosomes revealed that mephedrone and methylone are nonselective substrates for plasma membrane monoamine transporters, similar to MDMA in potency and selectivity. In vivo microdialysis in rat nucleus accumbens showed that i.v. administration of 0.3 and 1.0 mg/kg of mephedrone or methylone produces dose-related increases in extracellular dopamine and serotonin (5-HT), with the magnitude of effect on 5-HT being greater. Both methcathinone analogs were weak motor stimulants when compared with methamphetamine. Repeated administrations of mephedrone or methylone (3.0 and 10.0 mg/kg, s.c., 3 doses) caused hyperthermia but no long-term change in cortical or striatal amines, whereas similar treatment with MDMA (2.5 and 7.5 mg/kg, s.c., 3 doses) evoked robust hyperthermia and persistent depletion of cortical and striatal 5-HT. Our data demonstrate that designer methcathinone analogs are substrates for monoamine transporters, with a profile of transmitter-releasing activity comparable to MDMA. Dopaminergic effects of mephedrone and methylone may contribute to their addictive potential, but this hypothesis awaits confirmation. Given the widespread use of mephedrone and methylone, determining the consequences of repeated drug exposure warrants further study. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/22169943/The_designer_methcathinone_analogs_mephedrone_and_methylone_are_substrates_for_monoamine_transporters_in_brain_tissue_ L2 - http://dx.doi.org/10.1038/npp.2011.304 DB - PRIME DP - Unbound Medicine ER -