Phenmetrazine

Phenmetrazine

Systematic (IUPAC) name
3-methyl-2-phenylmorpholine
Clinical data
Legal status	CA: Schedule IV DE: Anlage II (Prohibited) UK: Class B US: Schedule II
Routes of administration	Oral, Intravenous, Vaporized, Insufflated, Suppository
Pharmacokinetic data
Biological half-life	8 hours
Excretion	Renal
Identifiers
CAS Number	134-49-6 Y
ATC code	none
PubChem	CID: 4762
DrugBank	DB00830 Y
ChemSpider	4598 Y
UNII	XA501VL3VR Y
KEGG	C07432 Y
ChEMBL	CHEMBL1201208 N
Chemical data
Formula	C11H15NO
Molecular mass	177.2456
SMILES CC1C(C2=CC=CC=C2)OCCN1
InChI InChI=1S/C11H15NO/c1-9-11(13-8-7-12-9)10-5-3-2-4-6-10/h2-6,9,11-12H,7-8H2,1H3 Y Key:OOBHFESNSZDWIU-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Phenmetrazine (INN, USAN, BAN) (brand name Preludin, and many others) is a stimulant drug that was previously used as an appetite suppressant, but has since been withdrawn from the market. It was initially replaced by its analogue phendimetrazine which functions as a prodrug to phenmetrazine, but now it is rarely prescribed, due to concerns of abuse and addiction. Chemically, phenmetrazine is a substituted amphetamine with a morpholine ring.

History

Phenmetrazine was first patented in Germany in 1952 by Boehringer-Ingelheim, 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.

Medical use

In clinical use, phenmetrazine produces less nervousness, hyperexcitability, euphoria and insomnia than drugs of the amphetamine family. It tends not to increase heart rate as much as other stimulants. Due to the relative lack of side effects, one study found it well tolerated in children. In a study of the effectiveness on weight loss between phenmetrazine and dextroamphetamine, phenmetrazine was found to be slightly more effective.

Pharmacology

Phenmetrazine acts as a releasing agent of norepinephrine and dopamine with EC₅₀ values of 50.4 ± 5.4 nM and 131 ± 11 nM, respectively. It has negligible efficacy as a releaser of serotonin, with an EC₅₀ value of only 7,765 ± 610 nM.

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.

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 4 times as effective in both methods of administration.

Chemistry

Its structure incorporates the backbone of amphetamine, the prototypical CNS stimulant which, like phenmetrazine, is a releasing agent of dopamine and norepinephrine. The molecule also loosely resembles ethcathinone, the active metabolite of popular anorectic amfepramone (diethylpropion). Unlike phenmetrazine, ethcathinone (and therefore amfepramone as well) are mostly selective as noradrenaline releasing agents.

Recreational use

Phenmetrazine has been used recreationally in many countries, for example 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. At first 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 "Prellies" (Preludin) 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 U.S.A. throughout the 1960s and early 1970s. It could be crushed up in water, heated and injected. The street name for the drug in Washington, D.C. was "Bam". More recently phenmetrazine has continued to be abused around the world, in countries such as South Korea.

See also

• Substituted phenylmorpholine
• 3-Benzhydrylmorpholine
• Fenbutrazate
• Edivoxetine
• Morazone
• Reboxetine
• The Beatles drug use in Hamburg
• 3-Fluorophenmetrazine