Abstract
Rationale
Synthetic cathinones continue to be sold as “legal” alternatives to methamphetamine or cocaine. As these marginally legal compounds become controlled, suppliers move to other, unregulated compounds.
Objectives
The purpose of these experiments was to determine whether several temporarily controlled cathinone compounds, which are currently abused on the street, stimulate motor activity and have discriminative stimulus effects similar to cocaine and/or methamphetamine.
Methods
Methcathinone, pentedrone, pentylone, 3-fluoromethcathinone (3-FMC), and 4-methylethcathinone (4-MEC) were tested for locomotor stimulant effects in mice and subsequently for substitution in rats trained to discriminate cocaine (10 mg/kg, i.p.) or methamphetamine (1 mg/kg, i.p.) from saline.
Results
Methcathinone, pentedrone, and pentylone produced locomotor stimulant effects which lasted up to 6 h. In addition, pentylone produced convulsions and lethality at 100 mg/kg. 4-MEC produced locomotor stimulant effects which lasted up to 2 h. Methcathinone, pentedrone, pentylone, 3-FMC, and 4-MEC each produced discriminative stimulus effects similar to those of cocaine and methamphetamine.
Conclusions
All of the tested compounds produce discriminative stimulus effects similar to either those of cocaine, methamphetamine, or both, which suggests that these compounds are likely to have similar abuse liability to cocaine and/or methamphetamine. Pentylone may be more dangerous on the street, as it produced adverse effects at doses that produced maximal stimulant-like effects.
Similar content being viewed by others
References
Araújo AM, Valente MJ, Carvalho M, Dias da Silva D, Gaspar H, Carvalho F, de Lourdes Bastos M, Guedes de Pinho P (2014) Raising awareness of new psychoactive substances: chemical analysis and in vitro toxicity screening of ‘legal high’ packages containing synthetic cathinones. Arch Toxicol
Bonano JS, Glennon RA, De Felice LJ, Banks ML, Negus SS (2014) Abuse-related and abuse-limiting effects of methcathinone and the synthetic “bath salts” cathinone analogs methylenedioxypyrovalerone (MDPV), methylone and mephedrone on intracranial self-stimulation in rats. Psychopharmacology (Berlin) 231:199–207
Bondareva TS, Young R, Glennon RA (2002) Central stimulants as discriminative stimuli. Asymmetric generalization between (−)ephedrine and S(+)methamphetamine. Pharmacol Biochem Behav 74:157–162
Calkins RF, Aktan GB, Hussain KL (1995) Methcathinone: the next illicit stimulant epidemic? J Psychoactive Drugs 27:277–285
Carroll FI, Blough BE, Abraham P, Mills AC, Holleman JA, Wolckenhauer SA, Decker AM, Landavazo A, McElroy KT, Navarro HA, Gatch MB, Forster MJ (2009) Synthesis and biological evaluation of bupropion analogues as potential pharmacotherapies for cocaine addiction. J Med Chem 52:6768–6781
Cozzi NV, Brandt SD, Daley PF, Partilla JS, Rothman RB, Tulzer A, Sitte HH, Baumann MH (2013) Pharmacological examination of trifluoromethyl ring-substituted methcathinone analogs. Eur J Pharmacol 699:180–187
Dal Cason TA, Young R, Glennon RA (1997) Cathinone: an investigation of several N-alkyl and methylenedioxy analogs. Pharmacol Biochem Behav 58:1109–1116
Drug Enforcement Administration DJ (2014) Schedules of controlled substances: temporary placement of 10 synthetic cathinones into Schedule I. Final order. Fed Regist 79:12938–12943
Elliott S, Evans J (2014) A 3-year review of new psychoactive substances in casework. Forensic Sci Int 243C:55–60
Emerson TS, Cisek JE (1993) Methcathinone: a Russian designer amphetamine infiltrates the rural midwest. Ann Emerg Med 22:1897–1903
Eshleman AJ, Wolfrum KM, Hatfield MG, Johnson RA, Murphy KV, Janowsky A (2013) Substituted methcathinones differ in transporter and receptor interactions. Biochem Pharmacol
Fantegrossi WE, Gannon BM, Zimmerman SM, Rice KC (2013) In vivo effects of abused ‘bath salt’ constituent 3,4-methylenedioxypyrovalerone (MDPV) in mice: drug discrimination, thermoregulation, and locomotor activity. Neuropsychopharmacol 38:563–573
Gatch MB, Forster MJ, Janowsky A, Eshleman AJ (2011) Abuse liability profile of three substituted tryptamines. J Pharmacol Exp Ther 338:280–289
Gatch MB, Taylor CM, Forster MJ (2013) Locomotor stimulant and discriminative stimulus effects of ‘bath salt’ cathinones. Behav Pharmacol 24:437–447
Gil D, Adamowicz P, Skulska A, Tokarczyk B, Stanaszek R (2013) Analysis of 4-MEC in biological and non-biological material—three case reports. Forensic Sci Int 228:e11–e15
Glennon RA (2014) Bath salts, mephedrone, and methylenedioxypyrovalerone as emerging illicit drugs that will need targeted therapeutic intervention. Adv Pharmacol 69:581–620
Glennon RA, Yousif M, Naiman N, Kalix P (1987) Methcathinone: a new and potent amphetamine-like agent. Pharmacol Biochem Behav 26:547–551
Kaminski BJ, Griffiths RR (1994) Intravenous self-injection of methcathinone in the baboon. Pharmacol Biochem Behav 47:981–983
Katz JL, Agoston GE, Alling KL, Kline RH, Forster MJ, Woolverton WL, Kopajtic TA, Newman AH (2001) Dopamine transporter binding without cocaine-like behavioral effects: synthesis and evaluation of benztropine analogs alone and in combination with cocaine in rodents. Psychopharmacology (Berl) 154:362–374
Kohut SJ, Fivel PA, Blough BE, Rothman RB, Mello NK (2013) Effects of methcathinone and 3-Cl-methcathinone (PAL-434) in cocaine discrimination or self-administration in rhesus monkeys. Int J Neuropsychopharmacol 16:1985–1998
Li SM, Campbell BL, Katz JL (2006) Interactions of cocaine with dopamine uptake inhibitors or dopamine releasers in rats discriminating cocaine. J Pharmacol Exp Ther 317:1088–1096
López-Arnau R, Martínez-Clemente J, Pubill D, Escubedo E, Camarasa J (2012) Comparative neuropharmacology of three psychostimulant cathinone derivatives: butylone, mephedrone and methylone. Br J Pharmacol 167:407–420
Marinetti LJ, Antonides HM (2013) Analysis of synthetic cathinones commonly found in bath salts in human performance and postmortem toxicology: method development, drug distribution and interpretation of results. J Anal Toxicol 37:135–146
Marusich JA, Grant KR, Blough BE, Wiley JL (2012) Effects of synthetic cathinones contained in “bath salts” on motor behavior and a functional observational battery in mice. Neurotoxicology 33:1305–1313
Meyer MR, Vollmar C, Schwaninger AE, Wolf E, Maurer HH (2012) New cathinone-derived designer drugs 3-bromomethcathinone and 3-fluoromethcathinone: studies on their metabolism in rat urine and human liver microsomes using GC-MS and LC-high-resolution MS and their detectability in urine. J Mass Spectrom 47:253–262
National Research Council (2011) Guide for the care and Use of laboratory animals, 8th edn. The National Academies Press, Washington, D.C
Schechter MD (1997a) Discriminative characteristics of high and low cocaine administration: effect of other psychostimulants. Pharmacol Biochem Behav 56:457–463
Schechter MD (1997b) Drug-drug discrimination: stimulus properties of drugs of abuse upon a serotonergic-dopaminergic continuum. Pharmacol Biochem Behav 56:89–96
Simmler LD, Rickli A, Hoener MC, Liechti ME (2014) Monoamine transporter and receptor interaction profiles of a new series of designer cathinones. Neuropharmacology 79:152–160
UNODC (2013) The challenge of new psychoactive substances. United Nations Office on Drugs and Crime, Vienna, Austria, pp 20131–108
Uralets V, Rana S, Morgan S, Ross W (2014) Testing for designer stimulants: metabolic profiles of 16 synthetic cathinones excreted free in human urine. J Anal Toxicol 38:233–241
van der Schoot JB, Ariens EJ, van Rossum JM, Hurkmans JATM (1962) Phenylisopropylamine derivatives, structure and action. Arznemittel-Forschung 12:902–907
Varner KJ, Daigle K, Weed PF, Lewis PB, Mahne SE, Sankaranarayanan A, Winsauer PJ (2012) Comparison of the behavioral and cardiovascular effects of mephedrone with other drugs of abuse in rats. Psychopharmacology (Berlin) 225:675–685
Young R, Glennon RA (1998) Discriminative stimulus effects of S(−)-methcathinone (CAT): a potent stimulant drug of abuse. Psychopharmacology (Berl) 140:250–256
Acknowledgments
Funding was provided by the Addiction Treatment Discovery Program of the National Institute on Drug Abuse (NIH N01DA-2-8822 and N01DA-13-8908). Program staff was involved in selection of compounds and test parameters. The ATDP had no further role in study design; the collection, analysis, and interpretation of data; or the writing of the report. They have granted permission for the submission of this data for publication.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gatch, M.B., Rutledge, M.A. & Forster, M.J. Discriminative and locomotor effects of five synthetic cathinones in rats and mice. Psychopharmacology 232, 1197–1205 (2015). https://doi.org/10.1007/s00213-014-3755-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-014-3755-3