Phenmetrazine

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among others, is a stimulant drug first synthesized in 1952 and originally used as an appetite suppressant, but withdrawn from the market in the 1980s due to widespread misuse.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.

Medical uses

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.

Pharmacology

Pharmacodynamics

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.