Phendimetrazine

Phendimetrazine
Clinical data
Trade names	Bontril
AHFS/Drugs.com	Monograph
Routes of; administration	By mouth
ATC code	none;
Legal status
Legal status	BR: Class B2 (Anorectic drugs); CA: Schedule IV; DE: Anlage II (Authorized trade only, not prescriptible); US: Schedule III;
Pharmacokinetic data
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
Identifiers
	IUPAC name 3,4-dimethyl-2-phenylmorpholine;
CAS Number	634-03-7 ;
PubChem CID	30487;
DrugBank	DB01579 ;
ChemSpider	28295 ;
UNII	AB2794W8KV;
KEGG	D08347 ;
ChEMBL	ChEMBL1615439 ;
CompTox Dashboard (EPA)	DTXSID1023447 ;
ECHA InfoCard	100.010.186
Chemical and physical data
Formula	C12H17NO
Molar mass	191.274 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@H]1[C@@H](OCCN1C)C2=CC=CC=C2;
	InChI InChI=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 ; Key:MFOCDFTXLCYLKU-CMPLNLGQSA-N ;
	(verify)

Phendimetrazine, sold under the brand name Bontril among others, is a stimulant medication of the morpholine chemical class used as an appetite suppressant.^[2]

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).^[3]

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. 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.^[4]

Synthesis

The reaction between N-methylethanolamine and 2-bromopropiophenone gives compound (3), which is reductively cyclized using formic acid to synthesize phendimetrazine.^[5]^[6]

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.

References

^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
^ Landau D, Jackson J, Gonzalez G (2008). "A case of demand ischemia from phendimetrazine". Cases J. 1 (1): 105. doi:10.1186/1757-1626-1-105. PMC 2531092. PMID 18710555.
^ Rothman RB, Baumann MH (2006). "Therapeutic potential of monoamine transporter substrates". Current Topics in Medicinal Chemistry. 6 (17): 1845–59. doi:10.2174/156802606778249766. PMID 17017961. Retrieved 5 May 2020.
^ "List of psychotropic substances under international control" (PDF). Archived from the original (PDF) on 31 August 2012. Retrieved 15 June 2005.
^ "Phendimetrazine". Thieme. Retrieved 30 June 2024.
^ Werner Heel and Karl Zeile, U.S. patent 2,997,469 (1961 to Ingelheim, Germany, assignors to C. H. Boehringer Sohn, Ingelheim, Germany, a partnership).

[1] Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.

[pmid18710555-2] Landau D, Jackson J, Gonzalez G (2008). "A case of demand ischemia from phendimetrazine". Cases J. 1 (1): 105. doi:10.1186/1757-1626-1-105. PMC 2531092. PMID 18710555.

[pmid17017961-3] Rothman RB, Baumann MH (2006). "Therapeutic potential of monoamine transporter substrates". Current Topics in Medicinal Chemistry. 6 (17): 1845–59. doi:10.2174/156802606778249766. PMID 17017961. Retrieved 5 May 2020.

[4] "List of psychotropic substances under international control" (PDF). Archived from the original (PDF) on 31 August 2012. Retrieved 15 June 2005.

[5] "Phendimetrazine". Thieme. Retrieved 30 June 2024.

[6] Werner Heel and Karl Zeile, U.S. patent 2,997,469 (1961 to Ingelheim, Germany, assignors to C. H. Boehringer Sohn, Ingelheim, Germany, a partnership).

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