| Revision as of 12:05, 5 December 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{drugbox}} taken from revid 456799834 of page Phenmetrazine for the Chem/Drugbox validation project (updated: 'ChEMBL'). |
Latest revision as of 05:19, 19 December 2024 edit Whywhenwhohow (talk | contribs)Autopatrolled, Extended confirmed users, Pending changes reviewers48,924 edits remove text without citation |
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{{Short description|Chemical compound}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{Use dmy dates|date=June 2024}} |
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{{Drugbox |
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{{cs1 config |name-list-style=vanc |display-authors=6}} |
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{{Infobox drug |
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| Verifiedfields = changed |
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| Watchedfields = changed |
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| verifiedrevid = 409759788 |
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| verifiedrevid = 464200421 |
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| IUPAC_name = 3-methyl-2-phenylmorpholine |
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| image = Phenmetrazine.svg |
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| image = Phenmetrazine.svg |
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| width = 125 |
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| width = 125 |
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| alt = |
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<!--Clinical data--> |
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<!-- Clinical data --> |
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| tradename = |
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| pronounce = |
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| tradename = Preludin, others |
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| legal_AU = |
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| Drugs.com = |
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| MedlinePlus = |
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| DailyMedID = <!-- DailyMed may use generic or brand name (generic name preferred) --> |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_AU_comment = |
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| pregnancy_category = |
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| routes_of_administration = ], ], ]d, ]d, ] |
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| class = |
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| ATC_prefix = None |
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| ATC_suffix = |
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| ATC_supplemental = |
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<!-- Legal status --> |
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| legal_AU = S8 |
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| legal_AU_comment = |
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| legal_BR = A3 |
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| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023 |access-date=16 August 2023 |publisher=] |language=pt-BR |publication-date=4 April 2023}}</ref> |
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| legal_CA = Schedule IV |
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| legal_CA = Schedule IV |
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| legal_CA_comment = |
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| legal_DE = Anlage II |
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| legal_DE_comment = |
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| legal_NZ = <!-- Class A, B, C --> |
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| legal_NZ_comment = |
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| legal_UK = Class B |
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| legal_UK = Class B |
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| legal_UK_comment = |
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| legal_US = Schedule II |
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| legal_US = Schedule II |
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| legal_status = |
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| legal_US_comment = |
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| legal_EU = |
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| routes_of_administration = Oral, ], ]d, ]d, ] |
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| legal_EU_comment = |
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| legal_UN = P II |
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| legal_UN_comment = |
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| legal_status = SE: Förteckning II |
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<!--Pharmacokinetic data--> |
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<!-- Pharmacokinetic data --> |
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| bioavailability = |
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| protein_bound = |
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| metabolism = |
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| metabolites = |
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| onset = |
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| elimination_half-life = 8 hours |
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| elimination_half-life = 8 hours |
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| duration_of_action = |
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| excretion = ] |
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| excretion = ] |
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<!--Identifiers--> |
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<!-- Identifiers --> |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 134-49-6 |
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| CAS_number = 134-49-6 |
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| ATC_prefix = none |
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| PubChem = 4762 |
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| PubChem = 4762 |
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| IUPHAR_ligand = |
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| DrugBank_Ref = {{drugbankcite|changed|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB00830 |
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| DrugBank = DB00830 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = C07432 |
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| KEGG = C07432 |
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| ChEBI = |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = <!-- blanked - oldvalue: 1201208 --> |
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| ChEMBL = 1201208 |
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| C=11 | H=15 | N=1 | O=1 |
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| NIAID_ChemDB = |
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| PDB_ligand = |
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| molecular_weight = 177.2456 |
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| synonyms = |
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| smiles = O2C(c1ccccc1)C(NCC2)C |
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| InChI = 1/C11H15NO/c1-9-11(13-8-7-12-9)10-5-3-2-4-6-10/h2-6,9,11-12H,7-8H2,1H3 |
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<!-- Chemical and physical data --> |
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| InChIKey = OOBHFESNSZDWIU-UHFFFAOYAX |
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| IUPAC_name = 3-methyl-2-phenylmorpholine |
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| C=11 | H=15 | N=1 | O=1 |
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| SMILES = CC1C(C2=CC=CC=C2)OCCN1 |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 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 |
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| StdInChI = 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 |
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| StdInChI_comment = |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = OOBHFESNSZDWIU-UHFFFAOYSA-N |
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| StdInChIKey = OOBHFESNSZDWIU-UHFFFAOYSA-N |
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| density = |
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| solubility = |
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| specific_rotation = |
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}} |
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}} |
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'''Phenmetrazine''' (], ], ]) (brand name '''Preludin''', and many others) is a ] ] first synthesized in 1952 and originally used as an ], but withdrawn from the market in the 1980s due to widespread ]. It was initially replaced by its ] ] (under the brand name Prelu-2) which functions as a ] to phenmetrazine, but now it is rarely prescribed, due to concerns of abuse and ]. Chemically, phenmetrazine is a ] containing a ] ring. |
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== History == |
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Phenmetrazine was first patented in ] in 1952 by ],<ref>{{cite patent | inventor = Boehringer A, Boehringer E | title= Improvements in or relating to the preparation of substituted morpholines | country = GB | number= 773780}}</ref><ref>{{cite patent| url= http://www.google.com/patents/US2835669 |country= US| status= patent |title= Process for the Production of Substituted Morpholines | number= 2835669 | gdate= 20 May 1958| fdate= 29 June 1953| inventor = Thomä O | assign1= C. H. Boehringer Sohn}}</ref> with some pharmacological data published in 1954.<ref name= thomae>{{cite journal| vauthors = Thomä O, Wick H | title=Über einige Tetrahydro-1,4-oxazine mit sympathicomimetischen Eigenschaften| journal=Arch. Exp. Pathol. Pharmakol.| volume=222| year=1954| issue=6| pages=540| doi=10.1007/BF00246905| s2cid=25143525}}</ref> It was the result of a search by Thomä and Wick for an ] drug without the side-effects of ].<ref name=martel>{{cite journal | vauthors = Martel A | title = Preludin (phenmetrazine) in the treatment of obesity | journal = Canadian Medical Association Journal | volume = 76 | issue = 2 | pages = 117–120 | date = January 1957 | pmid = 13383418 | pmc = 1823494 }}</ref> Phenmetrazine was introduced into ] use in 1954 in ].<ref name=kalant>{{cite book| vauthors = Kalant OJ | title=The Amphetamines: Toxicity and Addiction| year=1966| isbn=0-398-02511-8}}</ref> |
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== Medical use == |
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In clinical use, phenmetrazine produces less ], hyperexcitability, ] and ] than drugs of the amphetamine family.<ref name=jama>{{cite journal | vauthors = | title = Phenmetrazine hydrochloride | journal = Journal of the American Medical Association | volume = 163 | issue = 5 | pages = 357 | date = February 1957 | pmid = 13385162 }}</ref> It tends not to increase ] as much as other stimulants. Due to the relative lack of ]s, one study found it well tolerated in children.<ref name=martel /> In a study of the effectiveness on ] between phenmetrazine and ], phenmetrazine was found to be slightly more effective.<ref name=hampson>{{cite journal | vauthors = Hampson J, Loraine JA, Strong JA | title = Phenmetrazine and dexamphetamine in the management of obesity | journal = Lancet | volume = 1 | issue = 7137 | pages = 1265–1267 | date = June 1960 | pmid = 14399386 | doi = 10.1016/S0140-6736(60)92250-9 }}</ref> |
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== Pharmacology == |
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Phenmetrazine acts as a ] of ] and ] with ] values of 50.4 ± 5.4 nM and 131 ± 11 nM, respectively.<ref name="pmid17017961">{{cite journal | vauthors = Rothman RB, Baumann MH | title = Therapeutic potential of monoamine transporter substrates | journal = Current Topics in Medicinal Chemistry | volume = 6 | issue = 17 | pages = 1845–1859 | year = 2006 | pmid = 17017961 | doi = 10.2174/156802606778249766 | url = http://www.bentham-direct.org/pages/content.php?CTMC/2006/00000006/00000017/0004R.SGM | access-date = 5 May 2020 | url-status = usurped | archive-url = https://web.archive.org/web/20170326103021/http://www.bentham-direct.org/pages/content.php?CTMC%2F2006%2F00000006%2F00000017%2F0004R.SGM | archive-date = 26 March 2017 }}</ref> It has negligible efficacy as a releaser of ], with an EC<sub>50</sub> value of only 7,765 ± 610 nM.<ref name="pmid17017961"/> |
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After an oral dose, about 70% of the drug is ] from the body within 24 hours. About 19% of that is excreted as the unmetabolised drug and the rest as various ]s.<ref name=clarkes>{{cite book| title=Clarke's Analysis of Drugs and Poisons| vauthors = Moffat AC, Osselton MD, Widdop D| year = 2004| isbn=0-85369-473-7}}</ref> |
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In trials performed on rats, it has been found that after ] administration of phenmetrazine, both ]s are equally effective in reducing food intake, but in ] administration the ] isomer is more effective. In terms of central stimulation however, the dextro isomer is about 4 times as effective in both methods of administration.<ref name=engelhardt>{{cite journal| title=Studies of the Mechanism of the Anti-Appetite Action of Phenmetrazine| vauthors = Engelhardt A | journal=Biochem. Pharmacol.| volume=8| issue=1| pages=100| year=1961| doi=10.1016/0006-2952(61)90520-2}}</ref> |
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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 ] as well as time to peak onset, however, sustained-release formulations offer improved ] with a steady release of ] which results in a lower peak concentration in blood plasma. |
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==Synthesis== |
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] |
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Phenmetrazine can be synthesized in three steps from 2-bromopropiophenone and ]. The intermediate alcohol 3-methyl-2-phenylmorpholin-2-ol ('''1''') is converted to a fumarate salt ('''2''') with ], then reduced with ] to give phenmetrazine free base ('''3'''). The free base can be converted to the fumarate salt ('''4''') by reaction with fumaric acid.<ref name="WO2011146850A1">{{cite patent | inventor = Blough BE, Rothman R, Landavazo A, Page KM, Decker AM | assign1 = Research Triangle Institute, | country = WO | number = 2011146850 | title = Phenylmorpholines and analogues thereof |url=https://patents.google.com/patent/WO2011146850A1/ }} pages 51,54–55</ref> |
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==Chemistry== |
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Phenmetrazine's structure incorporates the backbone of ], the prototypical CNS stimulant which, like phenmetrazine, is a releasing agent of dopamine and norepinephrine. The molecule also loosely resembles ], the active metabolite of popular anorectic ] (diethylpropion). Unlike phenmetrazine, ethcathinone (and therefore amfepramone as well) are mostly selective as noradrenaline releasing agents. |
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== Recreational use == |
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Phenmetrazine has been used recreationally in many countries, including ]. When stimulant use first became prevalent in Sweden in the 1950s, phenmetrazine was preferred to ] and ] by users.<ref>{{cite web| url=http://www.druglibrary.org/schaffer/LIBRARY/studies/cu/CU39.html| title=The Swedish Experience| vauthors = Brecher EM | access-date=31 October 2009}}</ref> In the autobiographical novel ''Rush'' by ], intravenous phenmetrazine is described as the most euphoric and pro-sexual of the stimulants the author used. |
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Phenmetrazine was classified as a ] in Sweden in 1959, and was taken completely off the market in 1965. Formerly the illegal demand was satisfied by smuggling from ], and later ] 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. |
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Phenmetrazine was taken by ] early in their career. ] was one known user. McCartney's introduction to drugs started in ], ]. 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 ] (whose mother bought them). McCartney would usually take one, but ] would often take four or five.<ref name="Milesp66-67">{{cite book| vauthors = Miles B | title= Paul McCartney: Many Years from Now| year= 1998| pages= | publisher= H. Holt| isbn= 0-8050-5248-8| url-access= registration| url= https://archive.org/details/paulmccartneyman00mile_0/page/66}}</ref> ] asserted, in his 1968 biography of the band,<ref name="Davies78">{{cite book| author-link= Hunter Davies| vauthors = Davies H | title=The Beatles: The Authorized Biography| url= https://archive.org/details/beatlesauthorize00davi| url-access= registration| year=1968 |page=| publisher = New York, McGraw-Hill Book Co | isbn=0-07-015457-0}}</ref> 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. |
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] said he was on phenmetrazine at the time he killed ].<ref>{{cite book| vauthors = Ruby J |title= Testimony of Jack Ruby| volume= 5| publisher= US Government Printing Office| year= 1964| pages= 198–99}}</ref> |
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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".<ref>{{cite book |title=Rosa Lee |vauthors=Dash L |publisher=HarperCollins |year=1996 |page=108}}</ref> Phenmetrazine continues to be used and abused around the world, in countries including ].<ref>{{cite journal | vauthors = Choi H, Baeck S, Jang M, Lee S, Choi H, Chung H | title = Simultaneous analysis of psychotropic phenylalkylamines in oral fluid by GC-MS with automated SPE and its application to legal cases | journal = Forensic Science International | volume = 215 | issue = 1–3 | pages = 81–87 | date = February 2012 | pmid = 21377815 | doi = 10.1016/j.forsciint.2011.02.011 }}</ref> |
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== References == |
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{{Reflist}} |
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{{Stimulants}} |
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{{Anorectics}} |
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{{Monoamine releasing agents}} |
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{{Phenethylamines}} |
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{{Portal bar | Medicine}} |
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{{Authority control}} |
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