Phenmetrazine, sold under the brand name Preludin among others, is a stimulant drug first synthesized in 1952 and originally used as an appetite suppressant, but withdrawn from the market in the 1980s due to widespread misuse. It was initially replaced by its analogue phendimetrazine (under the brand name Prelu-2) which functions as a prodrug to phenmetrazine, but now it is rarely prescribed, due to concerns of misuse and addiction. Chemically, phenmetrazine is a substituted amphetamine containing a morpholine ring or a substituted phenylmorpholine.

Phenmetrazine has been used as an appetite suppressant for purposes of weight loss. It was used therapeutically for this indication at a dosage of 25 mg two or three times per day (or 50–75 mg/day total) in adults. Phenmetrazine has been found to produce similar weight loss to dextroamphetamine in people with obesity.

In addition to its appetite suppressant effects, phenmetrazine has been shown to produce very similar subjective psychostimulant effects to those of amphetamine and methamphetamine in clinical studies, although only about one-fifth to one-third of the potency of dextroamphetamine by weight.

Phenmetrazine acts as a norepinephrine–dopamine releasing agent (NDRA), with EC₅₀Tooltip half-maximal effective concentration values for induction of norepinephrine and dopamine release of 29–50 nM and 70–131 nM, respectively. It has very weak activity as a releaser of serotonin, with an EC₅₀ value of 7,765 to >10,000 nM. The drug is several times less potent than dextroamphetamine and dextromethamphetamine as an NDRA in vitro. This is in accordance with the higher doses required clinically.

In contrast to many other monoamine releasing agents (MRAs), phenmetrazine is inactive in terms of vesicular monoamine transporter 2 (VMAT2) actions. A few other MRAs have also been found to be inactive at VMAT2, such as phentermine and benzylpiperazine (BZP). These findings indicate that VMAT2 activity is non-essential for robust MRA actions.

Phenmetrazine does not appear to have been assessed at the trace amine-associated receptor 1 (TAAR1).

Phenmetrazine has been found to dose-dependently elevate brain dopamine levels in rodents in vivo. A 10 mg/kg i.v. dose of phenmetrazine increased nucleus accumbens dopamine levels by around 1,400% in rats. For comparison, dextroamphetamine 3 mg/kg i.p. increased striatal dopamine levels by about 5,000% in rats. On the other hand, the maximal increases in brain dopamine levels with phenmetrazine are similar to those with the proposed dopamine transporter (DAT) "inverse agonists" methylphenidate and cocaine (e.g., ~1,500%). Dopamine-releasing drugs that lack VMAT2 activity are theorized to produce much smaller maximal impacts on dopamine levels under experimental conditions than those which also act on VMAT2 like amphetamine. However, the pharmacological significance of these VMAT2 interactions in humans is unclear.

In trials performed on rats, it has been found that after subcutaneous administration of phenmetrazine, both optical isomers are equally effective in reducing food intake, but in oral administration the levo isomer is more effective. In terms of central stimulation however, the dextro isomer is about four times as effective in both methods of administration.