Page last updated: 2024-11-05

phendimetrazine

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Phendimetrazine is a sympathomimetic amine with anorectic properties. It is a Schedule IV controlled substance in the United States, meaning it has a low potential for abuse. It is used for short-term weight loss in obese individuals. Phendimetrazine works by stimulating the central nervous system, which leads to a decrease in appetite and an increase in metabolism. The synthesis of phendimetrazine involves several steps, including the reaction of 2-amino-4-phenylbutane with a benzoyl chloride derivative. Research on phendimetrazine focuses on its potential for weight loss, as well as its potential side effects. Studies have shown that phendimetrazine can be effective for weight loss, but it can also cause side effects such as insomnia, anxiety, and dry mouth. Phendimetrazine is generally not recommended for long-term use due to the potential for dependence and side effects. It is important to consult with a healthcare professional before taking phendimetrazine or any other weight loss medication.'

phendimetrazine: minor descriptor (66-86); file maintained to MORPHOLINES (66-86); on-line & INDEX MEDICUS search MORPHOLINES (66-86); RN given refers to parent cpd without isomeric designation [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID12460
CHEMBL ID1744
SCHEMBL ID49481
MeSH IDM0263376

Synonyms (28)

Synonym
d-2-phenyl-3,4-dimethylmorpholine
(+)-3,4-dimethyl-2-phenylmorpholine
morpholine,4-dimethyl-2-phenyl-, (+)-
antapentan
morpholine,4-dimethyl-2-phenyl-, (2s-trans)-
nsc169187
sedafamen
bacarate
(+)-phendimetrazine
3,4-dimethyl-2-phenylmorpholine
phendimetrazine
(2s,3s)-3,4-dimethyl-2-phenylmorpholine
bontril
morpholine, 3,4-dimethyl-2-phenyl-
hyrex
wehless
dyrexan
CHEMBL1744
(2s-trans)-3,4-dimethyl-2-phenylmorpholine
21784-30-5
AKOS006239792
3-phenyl-2-methylmorpholine
SCHEMBL49481
3,4-dimethyl-2-phenylmorpholine-, (+)- #
MFOCDFTXLCYLKU-UHFFFAOYSA-N
J-501031
(+)-2-phenyl-3,4-dimethylmorpholin
Q1649219

Research Excerpts

Overview

Phendimetrazine (PDM) is a schedule III anorectic agent that functions as both a low-potency monoamine-uptake inhibitor and as a prodrug for the monoamine releaser phenmetrazine. Phendimetra tartrate is a newer drug that acts as a central stimulant and indirectly acting sympathomimetic.

ExcerptReferenceRelevance
"Phendimetrazine is a clinically available schedule III anorectic that functions as a prodrug for phenmetrazine and thus may have lower abuse liability."( Effects of 14-day treatment with the schedule III anorectic phendimetrazine on choice between cocaine and food in rhesus monkeys.
Banks, ML; Blough, BE; Negus, SS, 2013
)
1.35
"Phendimetrazine (PDM) is a schedule III anorectic agent that functions as both a low-potency monoamine-uptake inhibitor and as a prodrug for the monoamine-releaser phenmetrazine (PM), and it may serve as a clinically available, effective, and safer alternative to d-amphetamine."( Effects of phendimetrazine treatment on cocaine vs food choice and extended-access cocaine consumption in rhesus monkeys.
Banks, ML; Blough, BE; Fennell, TR; Negus, SS; Snyder, RW, 2013
)
1.5
"Phendimetrazine is a clinically available anorectic and candidate medication for the treatment of cocaine addiction. "( Cocaine-like discriminative stimulus effects of phendimetrazine and phenmetrazine in rats.
Banks, ML; Bauer, CT; Blough, BE; Negus, SS, 2016
)
2.13
"Phendimetrazine is a prodrug for the monoamine releaser phenmetrazine-a drug with known abuse potential. "( Abuse Potential of Oral Phendimetrazine in Cocaine-dependent Individuals: Implications for Agonist-like Replacement Therapy.
Bolin, BL; Rush, CR; Sites, JP; Stoops, WW,
)
1.88
"Phendimetrazine (PDM) is a clinically available anorectic and a candidate pharmacotherapy for cocaine addiction. "( Dissociable effects of the prodrug phendimetrazine and its metabolite phenmetrazine at dopamine transporters.
Banks, ML; Blough, BE; DeFelice, LJ; Lazenka, MF; Negus, SS; Solis, E; Suyama, JA, 2016
)
2.15
"Phendimetrazine tartrate is a newer drug that acts as a central stimulant and indirectly acting sympathomimetic with a host of uses similar to the class amphetamines. "( Rare case of rhabdomyolysis with therapeutic doses of phendimetrazine tartrate.
Godkar, D; Kwiker, D; Lokhandwala, N; Yakoby, M,
)
1.82
"Phendimetrazine is an effective and widely prescribed appetite suppressant. "( Interaction of the anorectic medication, phendimetrazine, and its metabolites with monoamine transporters in rat brain.
Baumann, MH; Blough, BE; Dersch, CM; Katsnelson, M; Partilla, JS; Rothman, RB; Vu, N, 2002
)
2.02
"Phendimetrazine is an anorectic agent which recently has been detected in three medical examiner's cases. "( Fatality from illicit phendimetrazine use.
Gault, R; Hood, I; Mirchandani, H; Monforte, J, 1988
)
2.03

Toxicity

ExcerptReferenceRelevance
"Cocaine was safe and well tolerated during maintenance on a threefold range of phendimetrazine doses."( Safety and tolerability of intranasal cocaine during phendimetrazine maintenance.
Hays, LR; Lile, JA; Rayapati, AO; Rush, CR; Stoops, WW; Strickland, JC, 2016
)
0.91

Pharmacokinetics

Phendimetrazine may serve as a prodrug for the N-demethylated metabolite and potent dopamine/norepinephrine releaser phenmetrazine.

ExcerptReferenceRelevance
" This study examined the behavioral and pharmacokinetic profile of the Schedule III compound phendimetrazine, which may serve as a prodrug for the N-demethylated metabolite and potent dopamine/norepinephrine releaser phenmetrazine."( Role of phenmetrazine as an active metabolite of phendimetrazine: evidence from studies of drug discrimination and pharmacokinetics in rhesus monkeys.
Banks, ML; Blough, BE; Fennell, TR; Negus, SS; Snyder, RW, 2013
)
0.86
" Parallel pharmacokinetic studies in the same monkeys examined plasma phenmetrazine and phendimetrazine levels for correlation with cocaine-like discriminative stimulus effects."( Role of phenmetrazine as an active metabolite of phendimetrazine: evidence from studies of drug discrimination and pharmacokinetics in rhesus monkeys.
Banks, ML; Blough, BE; Fennell, TR; Negus, SS; Snyder, RW, 2013
)
0.87

Compound-Compound Interactions

ExcerptReferenceRelevance
"To evaluate the long-term impact of Medifast meal-replacement supplements (MMRS) combined with appetite suppressant medication (ASM) among participants who received 52 weeks of treatment."( Effectiveness of Medifast supplements combined with obesity pharmacotherapy: a clinical program evaluation.
DiBartolomeo, JJ; Foreyt, JP; Haddock, CK; Poston, WS; Warner, PO, 2008
)
0.35

Bioavailability

ExcerptReferenceRelevance
" The method was shown to be applicable to a single-dose bioavailability study."( GLC determination of phendimetrazine in human plasma, serum, or urine.
Levitt, MJ; Miksic, JR; Rudolph, GR, 1983
)
0.58

Dosage Studied

ExcerptRelevanceReference
"A 32-year-old man developed rhabdomyolysis after ingesting double the recommended dosage of phentermine for a week in addition to engaging in strenuous activity."( Rhabdomyolysis associated with phentermine.
Darko, W; Nasser, S; Noviasky, JA; Probst, LA; Steidl, KE, 2010
)
0.36
" After completing a cocaine self-administration dose-response curve, sessions were suspended and PDM was administered (1."( Attenuation of cocaine self-administration by chronic oral phendimetrazine in rhesus monkeys.
Blough, BE; Czoty, PW; Fennell, TR; Nader, MA; Snyder, RW, 2016
)
0.68
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (9)

Assay IDTitleYearJournalArticle
AID678717Inhibition of human CYP3A4 assessed as ratio of IC50 in absence of NADPH to IC50 for presence of NADPH using 7-benzyloxyquinoline as substrate after 30 mins2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID678715Inhibition of human CYP2D6 assessed as ratio of IC50 in absence of NADPH to IC50 for presence of NADPH using 4-methylaminoethyl-7-methoxycoumarin as substrate after 30 mins2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID678713Inhibition of human CYP2C9 assessed as ratio of IC50 in absence of NADPH to IC50 for presence of NADPH using 7-methoxy-4-trifluoromethylcoumarin-3-acetic acid as substrate after 30 mins2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID678712Inhibition of human CYP1A2 assessed as ratio of IC50 in absence of NADPH to IC50 for presence of NADPH using ethoxyresorufin as substrate after 30 mins2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID678716Inhibition of human CYP3A4 assessed as ratio of IC50 in absence of NADPH to IC50 for presence of NADPH using diethoxyfluorescein as substrate after 30 mins2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID588220Literature-mined public compounds from Kruhlak et al phospholipidosis modelling dataset2008Toxicology mechanisms and methods, , Volume: 18, Issue:2-3
Development of a phospholipidosis database and predictive quantitative structure-activity relationship (QSAR) models.
AID678722Covalent binding affinity to human liver microsomes assessed per mg of protein at 10 uM after 60 mins presence of NADPH2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID678714Inhibition of human CYP2C19 assessed as ratio of IC50 in absence of NADPH to IC50 for presence of NADPH using 3-butyryl-7-methoxycoumarin as substrate after 30 mins2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
AID678720Metabolic stability in human liver microsomes assessed as low signal/noise ratio (S/N of 1 to 10) by measuring GSH adduct formation at 100 uM after 90 mins by HPLC-MS analysis2012Chemical research in toxicology, Oct-15, Volume: 25, Issue:10
Preclinical strategy to reduce clinical hepatotoxicity using in vitro bioactivation data for >200 compounds.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (55)

TimeframeStudies, This Drug (%)All Drugs %
pre-199027 (49.09)18.7374
1990's6 (10.91)18.2507
2000's5 (9.09)29.6817
2010's16 (29.09)24.3611
2020's1 (1.82)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 60.55

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index60.55 (24.57)
Research Supply Index4.14 (2.92)
Research Growth Index4.76 (4.65)
Search Engine Demand Index116.83 (26.88)
Search Engine Supply Index2.36 (0.95)

This Compound (60.55)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials2 (3.33%)5.53%
Reviews2 (3.33%)6.00%
Case Studies13 (21.67%)4.05%
Observational0 (0.00%)0.25%
Other43 (71.67%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (1)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Behavioral Effects of Drugs (Inpatient): 31 (Cocaine and Phendimetrazine) [NCT02522325]Phase 130 participants (Actual)Interventional2015-08-31Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT02522325 (1) [back to overview]Number of Times Cocaine Was Selected in the Presence of a Monetary Reward Alternative

Number of Times Cocaine Was Selected in the Presence of a Monetary Reward Alternative

The reinforcing effects of cocaine were determined using a modified progressive ratio procedure in which subjects made 10 choices between a portion of each available cocaine dose and money (US$0.25). Reinforcing effects are measured for each cocaine dose during both phendimetrazine and placebo maintenance. (NCT02522325)
Timeframe: After at least seven days of maintenance placebo or target phendimetrazine dose

,
InterventionCocaine Choices (Mean)
0 mg Cocaine20 mg Cocaine40 mg Cocaine80 mg Cocaine
Phendimetrazine.243.93.835.03
Placebo.344.314.695.90

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