Behavioral effects of four novel synthetic cathinone analogs in rodents

Addiction Biology - Tập 26 Số 4 - 2021
Michael B. Gatch1, Ritu A. Shetty1, Nathalie Sumien1, Michael J. Forster1
1Pharmacology and Neuroscience University of North Texas Health Science Center Fort Worth Texas USA

Tóm tắt

Abstract

A new generation of novel cathinone compounds has been developed as stimulant substitutes to avoid drug control laws and detection of use by blood tests. Dipentylone, N‐ethylhexedrone, 4‐chloroethcathinone (4‐CEC), and 4′‐methyl‐α‐pyrrolidinohexiophenone (MPHP) were tested for in vivo psychostimulant‐like effects to assess their abuse liability. Locomotor activity was assessed in an open‐field assay using Swiss–Webster mice to screen for locomotor stimulant effects and to identify behaviorally‐active dose ranges, times of peak effect, and durations of action. Discriminative stimulus effects were assessed in separate groups of Sprague–Dawley rats trained to discriminate cocaine or methamphetamine from vehicle. Dipentylone, N‐ethylhexedrone, 4‐CEC, and MPHP dose‐dependently increased locomotor activity. Dipentylone, N‐ethylhexedrone, and MPHP produced maximal stimulant effects similar to cocaine and methamphetamine. 4‐CEC was less efficacious, producing peak stimulant effects of about 74% of that of methamphetamine. The compounds were less potent than methamphetamine and approximately equipotent with cocaine. The doses of cocaine, methamphetamine, dipentylone, and 4‐CEC that produced peak effects lasted 2 to 3 h, the peak dose of N‐ethylhexedrone lasted 4 h, and the peak dose of MPHP lasted 6 h. All four compounds fully substituted for the discriminative stimulus effects of methamphetamine and cocaine, although full substitution by 4‐CEC occurred at doses that substantially decreased response rate. Only 4‐CEC fully substituted for MDMA. These data provide evidence that the novel cathinone compounds dipentylone, N‐ethylhexedrone, 4‐CEC, and MPHP demonstrate potential for abuse as psychostimulants, given their ability to stimulate locomotor activity and their substitution for the discriminative stimulus effects of methamphetamine and cocaine.

Từ khóa


Tài liệu tham khảo

European Monitoring Centre for Drugs and Drug Addiction, 2018, European Drug Report 2018: Trends and Developments

United Nations Office on Drugs and Crime (UNODC), 2017, Global Synthetic Drugs Assessment: Amphetamine‐type Stimulants and New Psychoactive Substances

10.1002/hup.2610

John ME, 2014, Bath salts abuse leading to new onset psychosis and potential for violence, Clin Schizophr Relat Psychoses, 20, 1

10.1016/j.genhosppsych.2012.06.005

10.3109/00952990.2012.677890

Paillet‐Loilier M, 2014, Emerging drugs of abuse: current perspectives on substituted cathinones, Subst Abuse Rehabil, 26, 37

10.12659/AJCR.889381

10.3109/15563650.2011.590812

10.1016/S1570-0232(03)00043-6

10.1016/j.forsciint.2006.07.024

10.1016/j.forsciint.2011.02.026

10.1177/0269881120914213

10.1002/dta.2136

10.1007/s13181-019-00734-x

10.1016/j.chroma.2019.05.051

10.1016/j.forsciint.2019.03.002

10.1016/j.forsciint.2019.03.003

10.1007/s11419-016-0345-6

10.1002/hup.2621

Drug Enforcement Administration, Department of Justice, 2019, Schedules of controlled substances: temporary placement of N‐ethylhexedrone, α‐PHP, 4‐MEAP, MPHP, PV8, and 4‐chloro‐α‐PVP in Schedule I, Fed Regist, 84, 18423

10.1007/s00213-018-5059-5

10.1097/FBP.0b013e3283644d2e

National Research Council, 2011, Guide for the Care and Use of Laboratory Animals

10.1038/npp.2012.233

10.1016/j.neuropharm.2017.09.002

10.1016/j.neuro.2012.08.003

10.1007/s11419‐018‐0409‐x

10.1007/s12640‐018‐9973‐4

10.1016/j.drugalcdep.2017.07.041

10.1097/FBP.0b013e328364166d

10.1097/FBP.0000000000000237

10.1016/j.drugalcdep.2019.02.016

10.1124/jpet.115.223586

10.1007/s00213-014-3755-3

10.1007/s00213‐018‐5063‐9

10.1124/jpet.115.229559

10.1038/npp.2017.98

10.1007/s00213-017-4562-4

10.1007/s00213-017-4526-8

10.4303/jdar/236009

10.1016/j.drugalcdep.2015.02.002

10.1007/s00213-016-4444-1

10.1111/adb.12399

10.1007/s00213-017-4716-4

10.1016/j.neuropharm.2018.01.020

10.1097/FBP.0000000000000540

10.1097/FBP.0000000000000328

10.1007/7854_2016_18

Thông tin
Thông tin xuất bản

Addiction Biology

Tập 26 Số 4

Thông tin tác giả