3-Fluorophenmetrazine

3-Fluorophenmetrazine (also known as 3-FPM, 3-FPH and PAL-593) is a phenylmorpholine-based stimulant and fluorinated analogue of phenmetrazine that has been sold online as a designer drug.

Chemistry

3-Fluorophenmetrazine is a fluorinated analogue of phenmetrazine, a stimulant of the morpholine class.

3-Fluorophenmetrazine is a regioisomer of both 2-fluorophenmetrazine and 4-fluorophenmetrazine.

Pharmacology

3-FPM acts as a norepinephrine–dopamine releasing agent with EC50 values of 30 nM and 43 nM, respectively. It shows only negligible efficacy as a releaser of serotonin, with an EC50 value of 2558 nM.

3-FPM also inhibits uptake mediated by dopamine transporters and norepinephrine transporters in HEK293 cells with potencies comparable to cocaine (IC50 values <2.5 μM), but with less potent effects at serotonin transporters (IC50 values >80 μM).

At sufficient doses, 3-FPM is capable of reversing monoamine transporters, particularly transporters of the catecholamines dopamine and norepinephrine, and, to a much lesser degree, serotonin transporters, thereby releasing these neurotransmitters from the cytosol into the extracellular space, where they are active.

Evaluation of its metabolic pathway revealed N-oxidation, aryl hydroxylation and subsequent O-methylation, alkyl hydroxylation, oxidation, and degradation of the ethyl-bridge yielding the O/N-bis-dealkylated metabolite, combinations thereof and further glucuronidation or sulfations.

Legality

In the United States, 3-fluorophenmetrazine is not explicitly illegal at the federal level, but may be considered under the federal analogue act if intended for consumption as a structural analog of the Schedule II drug Phenmetrazine, but only if intended for human consumption.

On November 16, 2016, it became an illegal substance in the state of Virginia. As of 2019, it is also a schedule I substance in Virginia.