Phendimetrazine

Last updated
Phendimetrazine
Phendimetrazine.svg
Clinical data
Trade names Bontril
AHFS/Drugs.com Monograph
Pregnancy
category
  • C (US)
Routes of
administration
Oral
ATC code
  • none
Legal status
Legal status
Pharmacokinetic data
Bioavailability Peak plasma levels occur within 1 to 3 hours. Absorption is usually complete by 4 to 6 hours
Metabolism Hepatic
Elimination half-life 19-24 hours
Excretion Urinary elimination
Identifiers
  • 3,4-dimethyl-2-phenylmorpholine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.010.186 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C12H17NO
Molar mass 191.274 g·mol−1
3D model (JSmol)
  • O2C(c1ccccc1)C(N(C)CC2)C
  • 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 Yes check.svgY
  • Key:MFOCDFTXLCYLKU-UHFFFAOYSA-N Yes check.svgY
   (verify)

Phendimetrazine (Bontril, Adipost, Anorex-SR, Appecon, Melfiat, Obezine, Phendiet, Plegine, Prelu-2, Statobex) is a stimulant drug of the morpholine chemical class used as an appetite suppressant. [2]

Contents

Pharmacology

Phendimetrazine functions as a prodrug to 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

Synthesis (2-chloroethanol also works): Phendimetrazine synthesis.svg
Synthesis (2-chloroethanol also works):

Alkylation of ephedrine (1) with oxirane (2) gives the diol, N-(2-Hydroxyethyl) Pseudoephedrine [54275-43-3] [91688-17-4] (3). (The secondary nature of the amine in 1) eliminates the complication of dialkylation and thus the need to go through the amide.) Cyclization affords phendimetrazine (4).

Thieme Patents (Ex 2): Phendimetrazine synthesis 2.svg
Thieme Patents (Ex 2):

The halogenation of Propiophenone [93-55-0] (1) with bromine gives 2-Bromopropiophenone [2114-00-3] (2). Further reaction with N-Methylethanolamine [109-83-1] (3) goes on to five CID:232614 [902267-47-4] (4). Cyclization with formic acid completed the synthesis of phendimetrazine (5).

Patent: Phendimetrazine synthesis 3.svg
Patent:

The reaction between Ephedrine [299-42-3] (1) and ethyl chloroacetate [105-39-5] (2) in the presence of sodium hydride gives 4,5-dimethyl-6-phenylmorpholin-3-one, [5493-96-9] (3). The optional reduction of the lactam carbonyl with lithium aluminium hydride.

Additional method: [10]

See also

Phendimetrazine.jpg

Related Research Articles

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References

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  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.
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  10. https://eurekamag.com/research/031/845/031845550.php