Behavioral effects of four novel synthetic cathinone analogs in rodents.
Alkaloids
/ pharmacology
Animals
Central Nervous System Stimulants
/ pharmacology
Cocaine
/ pharmacology
Discrimination Learning
/ drug effects
Dose-Response Relationship, Drug
Locomotion
/ drug effects
Male
Methamphetamine
/ pharmacology
Mice
Rats
Rats, Sprague-Dawley
Synthetic Drugs
/ pharmacology
abuse liability
cathinones
drug discrimination
locomotor activity
psychostimulants
Journal
Addiction biology
ISSN: 1369-1600
Titre abrégé: Addict Biol
Pays: United States
ID NLM: 9604935
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
19
10
2020
received:
24
07
2020
accepted:
21
10
2020
pubmed:
7
11
2020
medline:
15
12
2021
entrez:
6
11
2020
Statut:
ppublish
Résumé
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.
Substances chimiques
Alkaloids
0
Central Nervous System Stimulants
0
Synthetic Drugs
0
Methamphetamine
44RAL3456C
cathinone
540EI4406J
Cocaine
I5Y540LHVR
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12987Subventions
Organisme : NIDA NIH HHS
ID : N01DA-18-8936
Pays : United States
Informations de copyright
© 2020 Society for the Study of Addiction.
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