Test purchase, synthesis and characterization of 3‐fluorophenmetrazine (3‐FPM) and differentiation from its ortho‐ and para‐substituted isomers

Abstract

The knowledge captured in patent and scientific research literature stimulates new ideas and fosters new drug development efforts. Manufacturers and entrepreneurs dedicated to the sale of ‘research chemicals’ and/or new psychoactive substances (NPS) also make use of access to information to identify, prepare, and launch a range of new substances. One of the most recent compounds to appear on the NPS market is the phenmetrazine analog 3‐fluorophenmetrazine (3‐FPM) which represents one of many phenylmorpholines designed to explore treatment options in areas such as obesity and drug dependence. The anorectic drug analogs phenmetrazine and phendimetrazine, used as prescription medicines before they were withdrawn, feature amphetamine‐like properties associated with monoamine release. Available data on 3‐FPM suggest that the effects might show mechanistic overlaps. This study describes the synthesis and extensive analytical characterization of 3‐FPM and its differentiation from synthesized ortho‐ and para‐ substituted isomers, 2‐FPM and 4‐FPM, respectively. This study was triggered by the purchase of five powdered samples advertised as 3‐FPM by five different Internet vendors based in the United Kingdom. The analytical data obtained for the vendor samples were consistent with the synthesized 3‐FPM standard and differentiation between all three isomers was possible. The presence of positional isomers and the absence of suitable reference material can cause difficulties in the day‐to‐day operation of forensic work and given the rate at which many of the newly emerging NPS appear on the market, a comprehensive approach is needed when attempting to decipher the identity of NPS arriving onto the drug market. Copyright © 2016 John Wiley & Sons, Ltd.

3-Fluorophenmetrazine, a fluorinated analogue of phenmetrazine: Studies on in vivo metabolism in rat and human, in vitro metabolism in human CYP isoenzymes and microbial biotransformation in Pseudomonas Putida and wastewater using GC and LC coupled to (HR)-MS techniques

“…The human urine sample presented with an equal amount of phenmetrazine and 3-FPM. The impurities from the positional isomers 2-FPM and 4-FPM, was not tested in present study, but was previously found not to be present in testpurchased 3-FPM powders from online vendors [2].…”

“…The main MBPs of 3-FPM in wastewater were the carboxy metabolite (8), while in P. putida TSB growth cultures it was the N-oxide (1). The main excretion product in rat was the aryl hydroxylated metabolites (2), and in human urine it was the unchanged drug, in line with previous studies showing a similar drug/metabolite pattern after administration of phenmetrazine to rats and humans, respectively [15]. Urinary excretion is the main excretion pathway of phenmetrazine [3], as 3-FPM is an analogue to phenmetrazine, urinary excretion is assumed to be the main route of excretion for 3-FPM making the NPS suitable for evaluation by WBE.…”

“…Finding NPS on the market is done by analyzing seizure compounds or actively buying new compounds as they are traded via the internet. 3-Fluorophenmetrazine (3-FPM) was detected in 2014 on the UK market as a research chemical, the structure from online purchased and synthesized 3-FPM was recently analyzed by hyphenated mass spectrometry (MS) techniques, and nuclear magnetic resonance (NMR) [2]. Its pharmacologic effects are assumed being similar to phenmetrazine, due to its structural similarity.…”

Novel psychoactive substances: overdose of 3-fluorophenmetrazine (3-FPM) and etizolam in a 33-year-old man

“…3-FPM, also known as PAL-593, first became available in 2014, and is a fluorinated version of phenmetrazine (figure 2A), an abused drug from the 1960s used as an appetite suppressant 6. 3-FPM acts as a norepinephine dopamine releasing agent and hence has stimulatory properties.…”

Acute kidney injury and critical limb ischaemia associated with the use of the so called “legal high” 3-fluorophenmetrazine

“…3-FPM is one of many phenylmorpholines designed to treat obesity or ameliorate drug dependence [4]. It is suggested that it has properties similar to amphetamines associated with monoamine release [5]. There are many unofficial reports of effects available on the internet, supplied by users.…”