Phenmetrazine

from Wikipedia, the free encyclopedia
Structural formula
Structural formula of phenmetrazine
General
Non-proprietary name Phenmetrazine
other names
  • 2-phenyl-3-methylmorpholine
  • 3-methyl-2-phenyltetrahydro-2 H -1,4-oxazine
  • Fenmetrazine
  • Delgaxite
  • Delgotrix
  • Gracidin
  • Linotrazine
  • Mefolin
  • Phenmetrazinum
Molecular formula C 11 H 15 NO
External identifiers / databases
CAS number 134-49-6
ECHA InfoCard 100,004,677
PubChem 4762
ChemSpider 4598
DrugBank DB00830
Wikidata Q3329406
Drug information
Drug class

Appetite suppressant , psychostimulant

properties
Molar mass 177.25 g mol −1
Melting point

138-140 ° C

safety instructions
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Phenmetrazine is a chemical compound from the group of amphetamines and morpholines . It was previously used as an appetite suppressant but is no longer available. It was also used as a drug because of its stimulating effect .

properties

Phenmetrazine is a sympathomimetic and acts on the central nervous system . As such, it dampens the feeling of appetite and hunger in the brain and indirectly activates the sympathetic activity, which among other things leads to increased alertness and reduced need for sleep as well as increased physical and mental stamina. Due to the euphoric effect, there is a risk of developing addiction . Phenmetrazine (including its salts) is regulated in Germany as a marketable, non-prescription narcotic ( Annex II to the Narcotics Act ). The substance was used pharmaceutically as phenmetrazine hydrochloride, a crystalline substance which melts at 182 ° C and 1 g is soluble in 0.4 ml of water. Another salt described is that of 8-chlorotheophylline , phenmetrazine teoclate.

3-Methyl-2-phenylmorpholine has two chiral carbon atoms, so that four isomers are possible. Phenmetrazine has been described as the racemic trans form.

Development history

Phenmetrazine was patented by Boehringer Ingelheim in 1958 . In 1954, pharmacological properties were described. The aim of the development was an appetite suppressant without the typical side effects of amphetamines. Clinical studies were conducted in Europe in 1954.

In Germany, phenmetrazine tablets came onto the market in 1954 after one year of testing as a preludin for the "treatment of obesity", and only six months after the market launch, the manufacturers learned of its use in lay circles to combat symptoms of fatigue. In 1955, a prescription for the drug was introduced in Germany, some states already regulated phenmetrazine in 1966 because of the danger of addiction. In Germany, too, phenmetrazine was later classified as a narcotic before it was withdrawn from the market in the 1970s because of life-threatening pulmonary hypertension .

synthesis

Syntheses for phenmetrazine and its derivatives are described. They start from propiophenone , which is brominated with bromine on the α-carbon in the first step . The reaction with monoethanolamine follows . The product of this reaction can be present as a hemiacetal or as an open-chain compound. The latter can be reduced to the diol by sodium borohydride . Acid catalyzed cyclization leads to the formation of the morpholine ring .

Phenmetrazine synthesis.svg

effect

Compared to other amphetamines, phenmetrazine causes less nervousness , excitability , euphoria , insomnia and a slowdown in the pulse rate in overweight people. In a study it was well tolerated by overweight children who took half a tablet twice a day, so that their appetite fell sharply and physical performance increased due to the growing need for physical activity. In a study comparing phenmetrazine and dextroamphetamine , phenmetrazine was found to be slightly more effective in reducing weight.

Phenmetrazine increased the release of norepinephrine and dopamine with an EC 50 of 50.4 ± 5.4 nM and 131 ± 11 nM, respectively. The effect on the release of serotonin is negligible at an EC 50 of 7.765 ± 610 nM. After oral ingestion, 70% of the phenmetrazine is excreted within 24 hours. Of this, about 19% are unmetabolized. While in animal experiments on rats both stereoisomers were equally effective in feeding after subcutaneous injection , the levoform is more effective after oral administration. With regard to the stimulation of the central nervous system , the levoform is about four times stronger for both routes of application. Phenmetrazine is structurally similar to ethcathinone , the active metabolite of the appetite suppressant amfepramone (diethylpropion), but which only acts selectively on the release of norepinephrine.

Use as a drug

Phenmetrazine has been used as a drug in many countries. When stimulant use first became more common in Sweden in the 1950s, consumers preferred phenmetrazine to amphetamine and methamphetamine . In the autobiographical novel Rush of Kim Wozencraft intravenous phenmetrazine is described as the euphorischste and pro-most sexual of the stimulants used by the author. Phenmetrazine was classified as a narcotic drug in Sweden in 1959 and was completely withdrawn from the market in 1965. The illegal demand was initially satisfied by smuggling from Germany, later also from Spain and Italy. Preludin tablets were first smuggled, but smugglers soon began importing raw phenmetrazine powder. Eventually, because of its greater availability, amphetamine became the dominant stimulant of abuse.

Phenmetrazine was taken by the Beatles early in their careers. A well-known user was Paul McCartney. McCartney's introduction to the world of drugs began in Hamburg and Germany. The Beatles had to play for hours, and they often got the drug (known as “prellies”) from the maid who cleaned their apartment, from German customers or from Astrid Kirchherr (whose mother bought them). McCartney usually took one, but John Lennon often took four or five. Hunter Davies claimed in his 1968 biography of the band that their use of such stimulants at the time was more a response to their need to stay awake and keep working than just a desire for kicks.

Jack Ruby said he was on phenmetrazine at the time of his murder of Lee Harvey Oswald.

Preludin was also used recreationally in the United States in the 1960s and early 1970s. It could be crushed, heated, and injected in water. The street name for the drug in Washington, DC was "Bam". Phenmetrazine continues to be used and abused around the world, including in countries like South Korea .

Trade names

The trade name for phenmetrazine hydrochloride (tablets) in the US, UK and Germany was Preludin . The combination of phenmetrazine teoclat with fenbutrazate was on the market in Germany as cafilon (coated tablets).

Individual evidence

  1. ↑ a b RÖMPP Lexikon Chemie, 10th edition, 1996-1999: Volume 4: M - Pk. P. 3248.
  2. ↑ a b Merck Index 14
  3. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  4. ↑ E. Mutschler: drug effects. 7th edition, 1996, WVG. P. 167 f.
  5. ↑ External identifiers or database links for phenmetrazine hydrochloride : CAS number: 1707-14-8, EC number: 216-950-6 , ECHA InfoCard: 100.015.409 , PubChem : 92159 , ChemSpider : 83204 , Wikidata : Q27107702 .
  6. ↑ External identifiers or database links to phenmetrazine teoclat : CAS number: 13931-75-4, EC number: 237-701-8 , ECHA InfoCard: 100.034.260 , PubChem : 84106 , ChemSpider : 75877 , Wikidata : Q27276355 .
  7. ↑ RB Franklin: The fate of phenmetrazine in man and animals with observations on amphetamine and norephedrine metabolism in tamarin monkeys . Doctoral thesis, University of London, 1974.
  8. ^ FH Clarke: cis- and trans-3-methyl-2-phenylmorpholines . Journal of Organic Chemistry, Volume 27 (1962), 3251-3253 ( PDF ).
  9. ↑ Boehringer, Albert; Boehringer, Ernst. "Improvements in or relating to the preparation of substituted morpholines" (GB773780).
  10. ↑ Patent US2835669A : Process for the production of substituted morpholines. Registered on June 29, 1953 , published May 20, 1958 , inventor: Otto Thoma. Priority (national Erstanmedung): July 1,, 1952 (DE).
  11. ↑ O Thomä, H Wick: About some tetrahydro-1,4-oxazines with sympathomimetic properties . In: Arch. Exp. Pathol. Pharmacol. . 222, 1954, p. 540.
  12. ^ A b Antonio Martel: Preludin (Phenmetrazine) in the Treatment of Obesity . In: Can. Med. Assoc. J. . 76, No. 2, 1957, pp. 117-20. PMID 13383418 . PMC 1823494 (free full text).
  13. ↑ Oriana Josseau Kalant: The Amphetamines: Toxicity and Addiction 1966, ISBN 0-398-02511-8 .
  14. ^ Spiegel Wie Champagner , Spiegel, March 2, 1960.
  15. ↑ a b Bombs on St. Pauli , Spiegel, February 14, 1966.
  16. ↑ Losing weight: more harm than good? For weight reduction in healthy overweight people , arzneitelegramm No. 12, 1999.
  17. ↑ Harry Auterhoff : Textbook of pharmaceutical chemistry . WVG, 1978, p. 413.
  18. ↑ Gavin McLaughlin, Michael H. Baumann, Pierce V. Kavanagh, Noreen Morris, John D. Power: Synthesis, analytical characterization, and monoamine transporter activity of the new psychoactive substance 4-methylphenmetrazine (4-MPM), with differentiation from its ortho - and meta - positional isomers . In: Drug Testing and Analysis . tape 10 , no. 9 , September 2018, p. 1404-1416 , doi : 10.1002 / dta.2396 , PMID 29673128 , PMC 7316143 (free full text) - ( wiley.com [accessed August 24, 2020]).
  19. ↑ Patent US20130203752 : Phenylmorpholines and analogues thereof. Published on May 20, 2011 , Inventors: Bruce E. Blough, Richard Rothman, Antonio Landavazo, Kevin M. Page, Ann Marie Decker. ‌
  20. ↑ PHENMETRAZINE hydrochloride. In: Journal of the American Medical Association. Volume 163, Number 5, February 1957, p. 357, PMID 13385162 .
  21. ↑ Hampson, J, JA Loraine, JA Strong: Phenmetrazine and Dexamphetamine in the Management of Obesity . In: The Lancet . 275, No. 7137, 1960, pp. 1265-7. doi : 10.1016 / S0140-6736 (60) 92250-9 . PMID 14399386 .
  22. ^ A b Rothman RB, Baumann MH: Therapeutic potential of monoamine transporter substrates . In: Current Topics in Medicinal Chemistry . 6, No. 17, 2006, pp. 1845-59. doi : 10.2174 / 156802606778249766 . PMID 17017961 .
  23. ^ Anthony C Moffat, M David Osselton and Brian Widdop: Clarke's Analysis of Drugs and Poisons , ISBN 0-85369-473-7 .
  24. ^ Engelhardt, A: Studies of the Mechanism of the Anti-Appetite Action of Phenmetrazine . In: Biochem. Pharmacol. . 8, No. 1, 1961, p. 100. doi : 10.1016 / 0006-2952 (61) 90520-2 .
  25. ^ Brecher, Edward M: The Swedish Experience . Retrieved October 31, 2009.
  26. ↑ Barry Miles: Paul McCartney: Many Years from Now 1998, ISBN 0-8050-5248-8 , pp.  66-67 .
  27. ^ Hunter Davies: The Beatles: The Authorized Biography . 1968. ISBN 0-07-015457-0 , p. 78.
  28. ↑ Jack Ruby: Testimony of Jack Ruby , Volume 5. US Government Printing Office, 1964, pp. 198-99.
  29. ↑ Leon Dash: Rosa Lee . HarperCollins, 1996, p. 109.
  30. ↑ Choi H, Baeck S, Jang M, Lee S, Choi H, Chung H: Simultaneous analysis of psychotropic phenylalkylamines in oral fluid by GC-MS with automated SPE and its application to legal cases . In: Forensic Science International . 215, No. 1-3, February 10, 2012, pp. 81-87. doi : 10.1016 / j.forsciint.2011.02.011 . PMID 21377815 .