PMID- 29673128
OWN - NLM
STAT- MEDLINE
DCOM- 20190220
LR  - 20231111
IS  - 1942-7611 (Electronic)
IS  - 1942-7603 (Print)
IS  - 1942-7603 (Linking)
VI  - 10
IP  - 9
DP  - 2018 Sep
TI  - Synthesis, analytical characterization, and monoamine transporter activity of the 
      new psychoactive substance 4-methylphenmetrazine (4-MPM), with differentiation 
      from its ortho- and meta- positional isomers.
PG  - 1404-1416
LID - 10.1002/dta.2396 [doi]
AB  - The availability of new psychoactive substances (NPS) on the recreational drug 
      market continues to create challenges for scientists in the forensic, clinical 
      and toxicology fields. Phenmetrazine (3-methyl-2-phenylmorpholine) and an array 
      of its analogs form a class of psychostimulants that are well documented in the 
      patent and scientific literature. The present study reports on two phenmetrazine 
      analogs that have been encountered on the NPS market following the introduction 
      of 3-fluorophenmetrazine (3-FPM), namely 4-methylphenmetrazine (4-MPM), and 
      3-methylphenmetrazine (3-MPM). This study describes the syntheses, analytical 
      characterization, and pharmacological evaluation of the positional isomers of 
      MPM. Analytical characterizations employed various chromatographic, 
      spectroscopic, and mass spectrometric platforms. Pharmacological studies were 
      conducted to assess whether MPM isomers might display stimulant-like effects 
      similar to the parent compound phenmetrazine. The isomers were tested for their 
      ability to inhibit uptake or stimulate release of tritiated substrates at 
      dopamine, norepinephrine and serotonin transporters using in vitro transporter 
      assays in rat brain synaptosomes. The analytical characterization of three vendor 
      samples revealed the presence of 4-MPM in two of the samples and 3-MPM in the 
      third sample, which agreed with the product label. The pharmacological findings 
      suggest that 2-MPM and 3-MPM will exhibit stimulant properties similar to the 
      parent compound phenmetrazine, whereas 4-MPM may display entactogen properties 
      more similar to 3,4-methylenedioxymethamphetamine (MDMA). The combination of test 
      purchases, analytical characterization, targeted organic synthesis, and 
      pharmacological evaluation of NPS and their isomers is an effective approach for 
      the provision of data on these substances as they emerge in the marketplace.
CI  - Copyright (c) 2018 John Wiley & Sons, Ltd.
FAU - McLaughlin, Gavin
AU  - McLaughlin G
AUID- ORCID: 0000-0002-2496-8396
AD  - Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre 
      for Health Sciences, St James's Hospital, Dublin, Ireland.
AD  - Forensic Science Ireland, Garda Headquarters, Dublin, Ireland.
FAU - Baumann, Michael H
AU  - Baumann MH
AD  - Designer Drug Research Unit, Intramural Research Program, National Institute on 
      Drug Abuse, National Institutes of Health, Baltimore, Maryland.
FAU - Kavanagh, Pierce V
AU  - Kavanagh PV
AD  - Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre 
      for Health Sciences, St James's Hospital, Dublin, Ireland.
FAU - Morris, Noreen
AU  - Morris N
AD  - Department of Life & Physical Sciences, Faculty of Science and Health, Athlone 
      Institute of Technology, Co., Westmeath, Ireland.
FAU - Power, John D
AU  - Power JD
AUID- ORCID: 0000-0003-0926-1621
AD  - Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre 
      for Health Sciences, St James's Hospital, Dublin, Ireland.
AD  - Forensic Science Ireland, Garda Headquarters, Dublin, Ireland.
FAU - Dowling, Geraldine
AU  - Dowling G
AD  - Department of Pharmacology and Therapeutics, School of Medicine, Trinity Centre 
      for Health Sciences, St James's Hospital, Dublin, Ireland.
AD  - Department of Life Sciences, School of Science, Sligo Institute of Technology, 
      Ireland.
FAU - Twamley, Brendan
AU  - Twamley B
AD  - School of Chemistry, Trinity College Dublin, Ireland.
FAU - O'Brien, John
AU  - O'Brien J
AD  - School of Chemistry, Trinity College Dublin, Ireland.
FAU - Hessman, Gary
AU  - Hessman G
AUID- ORCID: 0000-0003-1527-7056
AD  - School of Chemistry, Trinity College Dublin, Ireland.
FAU - Westphal, Folker
AU  - Westphal F
AD  - State Bureau of Criminal Investigation Schleswig-Holstein, Section 
      Narcotics/Toxicology, Kiel, Germany.
FAU - Walther, Donna
AU  - Walther D
AD  - Designer Drug Research Unit, Intramural Research Program, National Institute on 
      Drug Abuse, National Institutes of Health, Baltimore, Maryland.
FAU - Brandt, Simon D
AU  - Brandt SD
AUID- ORCID: 0000-0001-8632-5372
AD  - School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, 
      UK.
LA  - eng
GR  - ZIA DA000522/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
DEP - 20180523
PL  - England
TA  - Drug Test Anal
JT  - Drug testing and analysis
JID - 101483449
RN  - 0 (Central Nervous System Stimulants)
RN  - 0 (Designer Drugs)
RN  - 0 (Dopamine Plasma Membrane Transport Proteins)
RN  - 0 (Illicit Drugs)
RN  - 0 (Indicators and Reagents)
RN  - 0 (Norepinephrine Plasma Membrane Transport Proteins)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Sert1 protein, rat)
RN  - 0 (Slc6a2 protein, rat)
RN  - 0 (Vesicular Monoamine Transport Proteins)
RN  - XA501VL3VR (Phenmetrazine)
SB  - IM
MH  - Animals
MH  - Brain Chemistry/drug effects
MH  - Central Nervous System Stimulants/*analysis
MH  - Chromatography, High Pressure Liquid
MH  - Designer Drugs/*analysis
MH  - Dopamine Plasma Membrane Transport Proteins/analysis
MH  - Gas Chromatography-Mass Spectrometry
MH  - Illicit Drugs/*analysis
MH  - Indicators and Reagents
MH  - Isomerism
MH  - Magnetic Resonance Spectroscopy
MH  - Male
MH  - Mass Spectrometry
MH  - Norepinephrine Plasma Membrane Transport Proteins/analysis
MH  - Phenmetrazine/analogs & derivatives/*analysis
MH  - RNA-Binding Proteins/analysis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reference Standards
MH  - Synaptosomes/drug effects/metabolism
MH  - Vesicular Monoamine Transport Proteins/*drug effects
PMC - PMC7316143
MID - NIHMS1592073
OTO - NOTNLM
OT  - Fluorophenmetrazine
OT  - monoamine transporters
OT  - new psychoactive substances
OT  - phenmetrazine
OT  - psychostimulants
EDAT- 2018/04/20 06:00
MHDA- 2019/03/20 06:00
PMCR- 2020/06/25
CRDT- 2018/04/20 06:00
PHST- 2018/01/28 00:00 [received]
PHST- 2018/04/12 00:00 [revised]
PHST- 2018/04/13 00:00 [accepted]
PHST- 2018/04/20 06:00 [pubmed]
PHST- 2019/03/20 06:00 [medline]
PHST- 2018/04/20 06:00 [entrez]
PHST- 2020/06/25 00:00 [pmc-release]
AID - 10.1002/dta.2396 [doi]
PST - ppublish
SO  - Drug Test Anal. 2018 Sep;10(9):1404-1416. doi: 10.1002/dta.2396. Epub 2018 May 
      23.