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among others, is a stimulant drug first synthesized in 1952 and originally used as an appetite suppressant, but withdrawn from the market in the 1980s due to widespread misuse.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 25mg two or three times per day (or 50–75mg/day total) in adults.
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,
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| Dextromethamphetamine || 12.3–14.3 || 8.5–40.4 || 736–1,292 ||
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| (+)-Phenmetrazine || 37.5 || 87.4 || 3246 || A few other MRAs have also been found to be inactive at VMAT2, such as phentermine and benzylpiperazine (BZP).
Phenmetrazine has been found to dose-dependently elevate brain dopamine levels in rodents in vivo. 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%).
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.
Pharmacokinetics
After an oral dose, about 70% of the drug is excreted from the body within 24 hours. About 19% of that is excreted as the unmetabolised drug and the rest as various metabolites.
The salt which has been used for immediate-release formulations is phenmetrazine hydrochloride (Preludin). Sustained-release formulations were available as resin-bound, rather than soluble, salts. Both of these dosage forms share a similar bioavailability as well as time to peak onset, however, sustained-release formulations offer improved pharmacokinetics with a steady release of active ingredient which results in a lower peak concentration in blood plasma.
Chemistry
Phenmetrazine, also known as (2RS,3RS)-2-phenyl-3-methylmorpholine or as (2RS,3RS)-3-methyl-2-phenyltetrahydro-2H-1,4-oxazine, is a substituted phenylmorpholine. In addition, the activities of various phenmetrazine analogues and derivatives as monoamine releasing agent (MRA) have been described. with some pharmacological data published in 1954. It was the result of a search by Thomä and Wick for an anorectic drug without the side effects of amphetamine. Phenmetrazine was introduced into clinical use in 1954 in Europe.
Society and culture
Names
Phenmetrazine is the generic name of the drug and its , , and . It is also known by the brand name Preludin.
Recreational use
Phenmetrazine has been used recreationally in many countries, including Sweden. When stimulant use first became prevalent in Sweden in the 1950s, phenmetrazine was preferred to amphetamine and methamphetamine by users. In the autobiographical novel Rush by Kim Wozencraft, intravenous phenmetrazine is described as the most euphoric and pro-sexual of the stimulants the author used.
Phenmetrazine was classified as a narcotic in Sweden in 1959, and was taken completely off the market in 1965. Formerly the illegal demand was satisfied by smuggling from Germany, and later Spain and Italy. At first, Preludin tablets were smuggled, but soon the smugglers started bringing in raw phenmetrazine powder. Eventually amphetamine became the dominant stimulant of abuse because of its greater availability.
Phenmetrazine was taken by the Beatles early in their career. Paul McCartney was one known user. McCartney's introduction to drugs started in Hamburg, Germany. The Beatles had to play for hours, and they were often given the drug (referred to as "prellies") by the maid who cleaned their housing arrangements, German customers, or by Astrid Kirchherr (whose mother bought them). McCartney would usually take one, but John Lennon would often take four or five. Hunter Davies asserted, in his 1968 biography of the band, that their use of such stimulants then was in response to their need to stay awake and keep working, rather than a simple desire for kicks.
Jack Ruby said he was on phenmetrazine at the time he killed Lee Harvey Oswald.
Preludin was also used recreationally in the US throughout the 1960s and 1970s. It could be crushed up in water, heated and injected. The street name for the drug in Washington, DC was "Bam". Phenmetrazine continues to be used and abused around the world, in countries including South Korea.