PMID- 32536334
OWN - NLM
STAT- MEDLINE
DCOM- 20210730
LR  - 20210730
IS  - 1461-7285 (Electronic)
IS  - 0269-8811 (Linking)
VI  - 34
IP  - 7
DP  - 2020 Jul
TI  - Methylenedioxymethamphetamine-like discriminative stimulus effects of 
      pyrrolidinyl cathinones in rats.
PG  - 778-785
LID - 10.1177/0269881120914213 [doi]
AB  - BACKGROUND: Synthetic cathinone derivatives are used as alternatives both for 
      stimulant drugs such as cocaine and methamphetamine and for club drugs such as 
      3,4-methylenedioxymethamphetamine (MDMA), but little is known about their 
      MDMA-like subjective effects. METHODS: In order to determine their similarity to 
      MDMA, the discriminative stimulus effects of 10 pyrrolidinyl cathinones 
      (alpha-pyrrolidinopropiophenone, 4'-methyl-alpha-pyrrolidinopropiophenone (4'-MePPP), 
      alpha-pyrrolidinobutiophenone, 3',4'-methylenedioxy-alpha-pyrrolidinobutyrophenone 
      (MD-PBP), alpha-pyrrolidinovalerophenone, 3,4-methylenedioxy-pyrovalerone (MDPV), 
      alpha-pyrrolidinopentiothiophenone, napthylpyrovalerone (naphyrone), 
      alpha-pyrrolidinohexiophenone, and 4'-methyl-alpha-pyrrolidinohexiophenone (4'-MePHP)) 
      were assessed in Sprague-Dawley rats trained to discriminate 1.5 mg/kg racemic 
      +/--MDMA from vehicle. RESULTS: Compounds with no substitutions on the phenyl ring 
      and the thiophene produced 44-67% MDMA-appropriate responding. In contrast, the 
      substituted pyrrolidinyl cathinones produced a range of MDMA-appropriate 
      responding dependent upon the length of the alpha side chain. 4'-MePPP, with a 
      single carbon on the alpha position, produced 99.8% MDMA-appropriate responding, 
      MD-PBP (two carbons) produced 83%, naphyrone (three carbons) produced 71%, MDPV 
      (three carbons) produced, 66%, and 4'-MePHP (four carbons) produced 47%. 
      CONCLUSIONS: Many cathinone compounds have discriminative stimulus effects 
      similar to those of MDMA. However, the pyrrolidine substitution appears to reduce 
      serotonergic effects, with a commensurate decrease in MDMA-like effects. 
      Substitutions on the phenyl ring appear to be able to restore MDMA-like 
      responding, but only in compounds with short alpha side chains. These findings 
      agree with earlier findings of increasing dopaminergic effects and stronger 
      reinforcing effects with increasing side chain. Assessment of more compounds is 
      necessary to establish the replicability/robustness of this phenomenon. These 
      findings may be of use in predicting which compounds will have MDMA/club 
      drug-like effects versus psychostimulant-like effects.
FAU - Gatch, Michael B
AU  - Gatch MB
AUID- ORCID: 0000-0003-3474-211X
AD  - Pharmacology and Neuroscience, University of North Texas Health Science Center, 
      Fort Worth, USA.
FAU - Forster, Michael J
AU  - Forster MJ
AD  - Pharmacology and Neuroscience, University of North Texas Health Science Center, 
      Fort Worth, USA.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20200613
PL  - United States
TA  - J Psychopharmacol
JT  - Journal of psychopharmacology (Oxford, England)
JID - 8907828
RN  - 0 (Alkaloids)
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Illicit Drugs)
RN  - 0 (Psychotropic Drugs)
RN  - 0 (Pyrrolidines)
RN  - 540EI4406J (cathinone)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Alkaloids/chemistry/*pharmacology
MH  - Animals
MH  - Central Nervous System Stimulants/chemistry/pharmacology
MH  - Discrimination Learning/drug effects
MH  - Illicit Drugs/chemistry/pharmacology
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Psychotropic Drugs/chemistry/*pharmacology
MH  - Pyrrolidines/chemistry/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - Cathinones
OT  - MDMA
OT  - drug discrimination
OT  - entactogens
OT  - pyrrolidines
EDAT- 2020/06/17 06:00
MHDA- 2021/07/31 06:00
CRDT- 2020/06/16 06:00
PHST- 2020/06/17 06:00 [pubmed]
PHST- 2021/07/31 06:00 [medline]
PHST- 2020/06/16 06:00 [entrez]
AID - 10.1177/0269881120914213 [doi]
PST - ppublish
SO  - J Psychopharmacol. 2020 Jul;34(7):778-785. doi: 10.1177/0269881120914213. Epub 
      2020 Jun 13.