Phenmetrazine
Encyclopedia
Phenmetrazine is a stimulant
drug
of the morpholine
chemical class that was previously used as an appetite suppressant, but has since been withdrawn from the market.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.
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
.
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 effect
s, 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.
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 metabolite
s.
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.
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.
. 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.
Preludin was also used recreationally in the U.S.A. throughout the 1960s and early '70s. It could be crushed up in water, heated and injected. The street name for the drug in Washington, D.C. was "Bam".
Stimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
of the morpholine
Morpholine
Morpholine is an organic chemical compound having the chemical formula O2NH. This heterocycle, pictured at right, features both amine and ether functional groups. Because of the amine, morpholine is a base; its conjugate acid is called morpholinium...
chemical class that was previously used as an appetite suppressant, but has since been withdrawn from the market. It was initially replaced by its analogue phendimetrazine
Phendimetrazine
Phendimetrazine is a stimulant drug of the morpholine chemical class used as an appetite suppressant....
which functions as a prodrug
Prodrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
to phenmetrazine, but now it is rarely prescribed, due to concerns of abuse
Drug abuse
Substance abuse, also known as drug abuse, refers to a maladaptive pattern of use of a substance that is not considered dependent. The term "drug abuse" does not exclude dependency, but is otherwise used in a similar manner in nonmedical contexts...
and addiction.
History
Phenmetrazine was first patented in GermanyGermany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
in 1952 by Boehringer-Ingelheim
Boehringer-Ingelheim
C.H. Boehringer Sohn AG & Ko. KG is the parent company of Boehringer Ingelheim, which was founded in 1885 by Albert Boehringer in Ingelheim am Rhein. The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally...
, 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
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
.
Phenmetrazine was introduced into clinical
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
use in 1954 in Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
.
Medical use
In clinical use, phenmetrazine produces less nervousness, hyperexcitability, euphoriaEuphoria (emotion)
Euphoria is medically recognized as a mental and emotional condition in which a person experiences intense feelings of well-being, elation, happiness, ecstasy, excitement and joy...
and insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
than drugs of the amphetamine family. It tends not to increase heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
as much as other stimulants. Due to the relative lack of side effect
Adverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
s, one study found it well tolerated in children. In a study of the effectiveness on weight loss
Weight loss
Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...
between phenmetrazine and dextroamphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
, phenmetrazine was found to be slightly more effective.
Pharmacology
Phenmetrazine acts as a releasing agentReleasing agent
A releasing agent , or simply releaser, is a drug that induces the release of a neurotransmitter from the presynaptic neuron into the synapse, leading to an increase in the extracellular concentrations of the neurotransmitter. Many drugs use neurotransmitter release to exert their psychological and...
of norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
and dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
with EC50
EC50
The term half maximal effective concentration refers to the concentration of a drug, antibody or toxicant which induces a response halfway between the baseline and maximum after some specified exposure time...
values of 50.4 ± 5.4 nM and 131 ± 11 nM, respectively. It has negligible efficacy as a releaser of serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
, with an EC50 value of only 7,765 ± 610 nM.
After an oral dose, about 70% of the drug is excreted
Excretion
Excretion is the process by which waste products of metabolism and other non-useful materials are eliminated from an organism. This is primarily carried out by the lungs, kidneys and skin. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell...
from the body within 24 hours. About 19% of that is excreted as the unmetabolised drug and the rest as various metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
s.
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
Mouth
The mouth is the first portion of the alimentary canal that receives food andsaliva. The oral mucosa is the mucous membrane epithelium lining the inside of the mouth....
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.
Its structure incorporates the backbone of amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
, the prototypical CNS stimulant which, like phenmetrazine, is a releasing agent of dopamine and norepinephrine. The molecule also loosely resembles ethcathinone
Ethcathinone
Ethcathinone, also known as ethylpropion, is a stimulant drug of the phenethylamine, amphetamine, and cathinone chemical classes. It is an active metabolite of the prodrug diethylcathinone and is fully responsible for its effects...
, 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 SwedenSweden
Sweden , officially the Kingdom of Sweden , is a Nordic country on the Scandinavian Peninsula in Northern Europe. Sweden borders with Norway and Finland and is connected to Denmark by a bridge-tunnel across the Öresund....
. When stimulant use first became prevalent in Sweden in the 1950s
1950s
The 1950s or The Fifties was the decade that began on January 1, 1950 and ended on December 31, 1959. The decade was the sixth decade of the 20th century...
, phenmetrazine was preferred to amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
and methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...
by users. In the autobiographical novel "Rush" by Kim Wozencraft
Kim Wozencraft
Kim Wozencraft is an American author. She is best known as the author of the internationally best-selling novel Rush, on which a 1991 film directed by Lili Fini Zanuck and...
, intravenous phenmetrazine is described as the most euphoric and pro-sexual of the stimulants the author used.
Phenmetrazine was classified as a narcotic
Narcotic
The term narcotic originally referred medically to any psychoactive compound with any sleep-inducing properties. In the United States of America it has since become associated with opioids, commonly morphine and heroin and their derivatives, such as hydrocodone. The term is, today, imprecisely...
in Sweden in 1959, and was taken completely off the market in 1965. At first the illegal demand was satisfied by smuggling from Germany
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
, and later Spain
Spain
Spain , officially the Kingdom of Spain languages]] under the European Charter for Regional or Minority Languages. In each of these, Spain's official name is as follows:;;;;;;), is a country and member state of the European Union located in southwestern Europe on the Iberian Peninsula...
and Italy
Italy
Italy , officially the Italian Republic languages]] under the European Charter for Regional or Minority Languages. In each of these, Italy's official name is as follows:;;;;;;;;), is a unitary parliamentary republic in South-Central Europe. To the north it borders France, Switzerland, Austria and...
. 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
The Beatles
The Beatles were an English rock band, active throughout the 1960s and one of the most commercially successful and critically acclaimed acts in the history of popular music. Formed in Liverpool, by 1962 the group consisted of John Lennon , Paul McCartney , George Harrison and Ringo Starr...
early in their career. Paul McCartney
Paul McCartney
Sir James Paul McCartney, MBE, Hon RAM, FRCM is an English musician, singer-songwriter and composer. Formerly of The Beatles and Wings , McCartney is listed in Guinness World Records as the "most successful musician and composer in popular music history", with 60 gold discs and sales of 100...
was one known user. McCartney's introduction to drugs started in Hamburg
Hamburg
-History:The first historic name for the city was, according to Claudius Ptolemy's reports, Treva.But the city takes its modern name, Hamburg, from the first permanent building on the site, a castle whose construction was ordered by the Emperor Charlemagne in AD 808...
, Germany
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
. 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
Astrid Kirchherr
Astrid Kirchherr is a German photographer and artist and is well known for her association with The Beatles and her photographs of The Beatles during their Hamburg days....
(whose mother bought them). McCartney would usually take one, but John Lennon
John Lennon
John Winston Lennon, MBE was an English musician and singer-songwriter who rose to worldwide fame as one of the founding members of The Beatles, one of the most commercially successful and critically acclaimed acts in the history of popular music...
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.
Preludin was also used recreationally in the U.S.A. throughout the 1960s and early '70s. It could be crushed up in water, heated and injected. The street name for the drug in Washington, D.C. was "Bam".