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DARK Classics in Chemical Neuroscience: Cathinone-Derived Psychostimulants.
ACS Chem Neurosci. 2018 10 17; 9(10):2379-2394.AC

Abstract

Cathinone is a plant alkaloid found in khat leaves of perennial shrubs grown in East Africa. Similar to cocaine, cathinone elicits psychostimulant effects which are in part attributed to its amphetamine-like structure. Around 2010, home laboratories began altering the parent structure of cathinone to synthesize derivatives with mechanisms of action, potencies, and pharmacokinetics permitting high abuse potential and toxicity. These "synthetic cathinones" include 4-methylmethcathinone (mephedrone), 3,4-methylenedioxypyrovalerone (MDPV), and the empathogenic agent 3,4-methylenedioxymethcathinone (methylone) which collectively gained international popularity following aggressive online marketing as well as availability in various retail outlets. Case reports made clear the health risks associated with these agents and, in 2012, the Drug Enforcement Agency of the United States placed a series of synthetic cathinones on Schedule I under emergency order. Mechanistically, cathinone and synthetic derivatives work by augmenting monoamine transmission through release facilitation and/or presynaptic transport inhibition. Animal studies confirm the rewarding and reinforcing properties of synthetic cathinones by utilizing self-administration, place conditioning, and intracranial self-stimulation assays and additionally show persistent neuropathological features which demonstrate a clear need to better understand this class of drugs. This Review will thus detail (i) historical context of cathinone use and the rise of "dark" synthetic derivatives, (ii) structural features and mechanisms of synthetic cathinones, (iii) behavioral effects observed clinically and in animals under controlled laboratory conditions, and (iv) neurotransmitters and circuits that may be targeted to manage synthetic cathinone abuse in humans.

Authors+Show Affiliations

Center for Substance Abuse Research (CSAR) , Lewis Katz School of Medicine at Temple University , Philadelphia , Pennsylvania 19140 , United States.Department of Psychology , Arizona State University , Tempe , Arizona 85281 , United States.Center for Substance Abuse Research (CSAR) , Lewis Katz School of Medicine at Temple University , Philadelphia , Pennsylvania 19140 , United States.Center for Substance Abuse Research (CSAR) , Lewis Katz School of Medicine at Temple University , Philadelphia , Pennsylvania 19140 , United States.Center for Substance Abuse Research (CSAR) , Lewis Katz School of Medicine at Temple University , Philadelphia , Pennsylvania 19140 , United States.Center for Substance Abuse Research (CSAR) , Lewis Katz School of Medicine at Temple University , Philadelphia , Pennsylvania 19140 , United States.Department of Psychology , Arizona State University , Tempe , Arizona 85281 , United States.

Pub Type(s)

Historical Article
Journal Article
Research Support, N.I.H., Extramural
Review

Language

eng

PubMed ID

29714473

Citation

Simmons, Steven J., et al. "DARK Classics in Chemical Neuroscience: Cathinone-Derived Psychostimulants." ACS Chemical Neuroscience, vol. 9, no. 10, 2018, pp. 2379-2394.
Simmons SJ, Leyrer-Jackson JM, Oliver CF, et al. DARK Classics in Chemical Neuroscience: Cathinone-Derived Psychostimulants. ACS Chem Neurosci. 2018;9(10):2379-2394.
Simmons, S. J., Leyrer-Jackson, J. M., Oliver, C. F., Hicks, C., Muschamp, J. W., Rawls, S. M., & Olive, M. F. (2018). DARK Classics in Chemical Neuroscience: Cathinone-Derived Psychostimulants. ACS Chemical Neuroscience, 9(10), 2379-2394. https://doi.org/10.1021/acschemneuro.8b00147
Simmons SJ, et al. DARK Classics in Chemical Neuroscience: Cathinone-Derived Psychostimulants. ACS Chem Neurosci. 2018 10 17;9(10):2379-2394. PubMed PMID: 29714473.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - DARK Classics in Chemical Neuroscience: Cathinone-Derived Psychostimulants. AU - Simmons,Steven J, AU - Leyrer-Jackson,Jonna M, AU - Oliver,Chicora F, AU - Hicks,Callum, AU - Muschamp,John W, AU - Rawls,Scott M, AU - Olive,M Foster, Y1 - 2018/05/11/ PY - 2018/5/2/pubmed PY - 2019/11/19/medline PY - 2018/5/2/entrez KW - Addiction KW - cathinone KW - designer drugs KW - dopamine KW - novel psychoactive substance(s) KW - reward KW - synthetic cathinone(s) SP - 2379 EP - 2394 JF - ACS chemical neuroscience JO - ACS Chem Neurosci VL - 9 IS - 10 N2 - Cathinone is a plant alkaloid found in khat leaves of perennial shrubs grown in East Africa. Similar to cocaine, cathinone elicits psychostimulant effects which are in part attributed to its amphetamine-like structure. Around 2010, home laboratories began altering the parent structure of cathinone to synthesize derivatives with mechanisms of action, potencies, and pharmacokinetics permitting high abuse potential and toxicity. These "synthetic cathinones" include 4-methylmethcathinone (mephedrone), 3,4-methylenedioxypyrovalerone (MDPV), and the empathogenic agent 3,4-methylenedioxymethcathinone (methylone) which collectively gained international popularity following aggressive online marketing as well as availability in various retail outlets. Case reports made clear the health risks associated with these agents and, in 2012, the Drug Enforcement Agency of the United States placed a series of synthetic cathinones on Schedule I under emergency order. Mechanistically, cathinone and synthetic derivatives work by augmenting monoamine transmission through release facilitation and/or presynaptic transport inhibition. Animal studies confirm the rewarding and reinforcing properties of synthetic cathinones by utilizing self-administration, place conditioning, and intracranial self-stimulation assays and additionally show persistent neuropathological features which demonstrate a clear need to better understand this class of drugs. This Review will thus detail (i) historical context of cathinone use and the rise of "dark" synthetic derivatives, (ii) structural features and mechanisms of synthetic cathinones, (iii) behavioral effects observed clinically and in animals under controlled laboratory conditions, and (iv) neurotransmitters and circuits that may be targeted to manage synthetic cathinone abuse in humans. SN - 1948-7193 UR - https://www.unboundmedicine.com/medline/citation/29714473/DARK_Classics_in_Chemical_Neuroscience:_Cathinone_Derived_Psychostimulants_ L2 - https://dx.doi.org/10.1021/acschemneuro.8b00147 DB - PRIME DP - Unbound Medicine ER -