Phendimetrazine
{{Short description|Pharmaceutical drug}}
{{redirect|Mephenmetrazine|other methyl substitutions of phenmetrazine|Phenmetrazine#Substituted phenmetrazines}}
{{Use dmy dates|date=September 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Drugbox
| verifiedrevid = 464200059
| image = Phendimetrazine.svg
| image_class = skin-invert-image
| width = 150
| alt =
| image2 = PhendimetrazineMV.png
| width2 = 200
| tradename = Bontril
| Drugs.com = {{drugs.com|monograph|bontril}}
| pregnancy_category =
| routes_of_administration = Oral administration
| legal_BR = B2
| legal_BR_comment = {{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=Diário Oficial da União |language=pt-BR |publication-date=4 April 2023}}
| legal_CA = Schedule IV
| legal_US = Schedule III
| legal_DE = Anlage II
| bioavailability = Peak plasma levels occur within 1 to 3 hours. Absorption is usually complete by 4 to 6 hours
| metabolism = Liver
| elimination_half-life = 19-24 hours
| excretion = Urinary elimination
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 634-03-7
| ATC_prefix = none
| ATC_suffix =
| PubChem = 30487
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01579
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 28295
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = AB2794W8KV
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08347
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1615439
| synonyms = Mephenmetrazine; (2S,3S)-3,4-Dimethyl-2-phenylmorpholine
| IUPAC_name = 3,4-dimethyl-2-phenylmorpholine
| C = 12
| H = 17
| N = 1
| O = 1
| smiles = C[C@H]1[C@@H](OCCN1C)C2=CC=CC=C2
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C12H17NO/c1-10-12(14-9-8-13(10)2)11-6-4-3-5-7-11/h3-7,10,12H,8-9H2,1-2H3/t10-,12+/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = MFOCDFTXLCYLKU-CMPLNLGQSA-N
}}
Phendimetrazine, sold under the brand name Bontril among others, is a stimulant medication of the morpholine chemical class used as an appetite suppressant.{{cite journal |vauthors=Landau D, Jackson J, Gonzalez G |title=A case of demand ischemia from phendimetrazine |journal=Cases J |volume=1 |issue=1 |pages=105 |year=2008 |pmid=18710555 |pmc=2531092 |doi=10.1186/1757-1626-1-105 |doi-access=free }}
Pharmacology
Phendimetrazine functions as a prodrug of phenmetrazine; approximately 30 percent of an oral dose is converted into it. Phendimetrazine can essentially be thought of as an extended-release formulation of phenmetrazine with less potential for abuse. Phendimetrazine is an anorectic drug which acts as a norepinephrine-dopamine releasing agent (NDRA).{{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 = 1845–59 | year = 2006 | pmid = 17017961 | doi = 10.2174/156802606778249766 | url = https://zenodo.org/record/1235860 | access-date = 5 May 2020 | archive-url = | archive-date = | url-status = }}
As an amphetamine congener, its structure incorporates the backbone of methamphetamine, a potent CNS stimulant. While the addition of an N-methyl group to amphetamine significantly increases its potency and bioavailability, methylation of phenmetrazine renders the compound virtually inactive. However, phendimetrazine is a prodrug for phenmetrazine which acts as the active metabolite. Phendimetrazine possesses preferable pharmacokinetics over phenmetrazine as a therapeutic agent because its metabolization by demethylases produces a more steady and prolonged exposure of active drug within the body.{{cite journal | vauthors = Banks ML, Blough BE, Fennell TR, Snyder RW, Negus SS | title = Role of phenmetrazine as an active metabolite of phendimetrazine: evidence from studies of drug discrimination and pharmacokinetics in rhesus monkeys | journal = Drug and Alcohol Dependence | volume = 130 | issue = 1-3 | pages = 158–166 | date = June 2013 | pmid = 23211394 | doi = 10.1016/j.drugalcdep.2012.10.026 | pmc = 3616150 }} This decreases abuse potential as the peak blood-concentration of active phenmetrazine that's produced from a single dose of phendimetrazine is lower than a single therapeutically equivalent dose of phenmetrazine.
Indicated as a short-term secondary treatment for exogenous obesity, phendimetrazine immediate-release 35mg tablets are typically consumed one hour before meals, not to exceed three doses daily. Phendimetrazine is also manufactured as a 105mg extended-release capsule for once daily dosing, typically consumed 30 to 60 minutes before a morning meal. Whereas the immediate-release formulation has a maximum daily dosage of 210mg (6 tablets), the extended-release capsules have a maximum daily dosage of 105mg (one capsule).
Legality
According to the List of Psychotropic Substances under International Control published by the International Narcotics Control Board, phendimetrazine is a Schedule III controlled substance under the Convention on Psychotropic Substances.{{Cite web |url=http://www.incb.org/pdf/e/list/green.pdf |title=List of psychotropic substances under international control |access-date=15 June 2005 |archive-date=31 August 2012 |archive-url=https://web.archive.org/web/20120831222336/http://www.incb.org/pdf/e/list/green.pdf |url-status=dead }}
Synthesis
:File:Phendimetrazine synthesis 2.svg
The reaction between N-methylethanolamine and 2-bromopropiophenone gives compound (3), which is reductively cyclized using formic acid to synthesize phendimetrazine.{{cite web |title=Phendimetrazine |url=https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-16-0068 |publisher=Thieme |access-date=30 June 2024}}Werner Heel and Karl Zeile, {{US patent|2997469}} (1961 to Ingelheim, Germany, assignors to C. H. Boehringer Sohn, Ingelheim, Germany, a partnership).
Society and culture
= Brand names =
It is sold under various brand names including Bontril, Bontril PDM, Adipost, Anorex-SR, Appecon, Melfiat, Obezine, Phendiet, Plegine, Prelu-2, and Statobex.{{Cite web |title=Phendimetrazine Tartrate (Phendimetrazine Tartrate): Side Effects, Uses, Dosage, Interactions, Warnings |url=https://www.rxlist.com/phendimetrazine-tartrate-drug.htm |access-date=2025-05-23 |website=RxList |language=en}} {{Cite web | title=Phendimetrazine (oral route) | url=https://www.mayoclinic.org/drugs-supplements/phendimetrazine-oral-route/description/drg-20075140 |access-date=2025-06-29 |website = Mayo Clinic}}
References
{{Reflist}}
{{Stimulants}}
{{Anorectics}}
{{Monoamine releasing agents}}
{{Phenethylamines}}
Category:Beta-Hydroxyamphetamines