PHENDIMETRAZINE

First approved in 1961

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C12H17NO
Molecular Weight	191.2695
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@H]1[C@@H](OCCN1C)C2=CC=CC=C2

InChI

InChIKey=MFOCDFTXLCYLKU-CMPLNLGQSA-N

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

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/018074s034lbl.pdf
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/pro/phendimetrazine.html | http://www.wikidoc.org/index.php/Phendimetrazine

Phendimetrazine is an appetite suppressant that is FDA approved for the treatment of exogenous obesity. It is clinically available anorectic agent, which display minimal interactions with monoamine transporters in vitro. On the other hand, their medications is known to be psychomotor stimulants when administered in vivo as indicated by their shared properties with illicit drugs like cocaine. The following adverse reactions are described, or described in greater detail, in other sections: Primary pulmonary hypertension; Valvular heart disease; Effect on the ability to engage in potentially hazardous tasks; Withdrawal effects following prolonged high dosage administration. Use of phendimetrazine tartrate is contraindicated during or within 14 days following the administration of monoamine oxidase inhibitors because of the risk of hypertensive crisis.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dopamine transporter 180 Target ID: CHEMBL238 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27514281	Blocker 537		2.56 µM [EC50]
Norepinephrine transporter 191 Target ID: CHEMBL222 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17017961	Blocker 537		8.3 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Exogenous obesity 19 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/018074s034lbl.pdf	Primary		Approved 8429	PHENDIMETRAZINE TARTRATE Approved Use Phendimetrazine tartrate is indicated in the management of exogenous obesity as a short term adjunct (a few weeks) in a regimen of weight reduction based on caloric restriction in patients with an initial body mass index (BMI) of 30 kg/m2 or higher who have not responded to appropriate weight reducing regimen (diet and/or exercise) alone. Below is a chart of Body Mass Index (BMI) based on various heights and weights. BMI is calculated by taking the patient’s weight, in kilograms (kg), divided by the patient’s height, in meters (m), squared. Metric conversions are as follows: pounds ÷ 2.2 = kg; inches x 0.0254 = meters. BODY MASS INDEX (BMI), kg/m2 Height (feet, inches) Weight(pounds) 5’0” 5’3” 5’6” 5’9” 6’0” 6’3” 140 27 25 23 21 19 18 150 29 27 24 22 20 19 160 31 28 26 24 22 20 170 33 30 28 25 23 21 180 35 32 29 27 25 23 190 37 34 31 28 26 24 200 39 36 32 30 27 25 210 41 37 34 31 29 26 220 43 39 36 33 30 28 230 45 41 37 34 31 29 240 47 43 39 36 33 30 250 49 44 40 37 34 31 Phendimetrazine tartrate is indicated for use as monotherapy only. Launch Date 1979

C_max

Value	Dose	Analyte	Population
1227 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23211394	3.2 mg/kg single, intramuscular dose: 3.2 mg/kg route of administration: Intramuscular experiment type: SINGLE co-administered:	PHENDIMETRAZINE plasma	Macaca mulatta population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
137 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23211394	0.32 mg/kg single, intramuscular dose: 0.32 mg/kg route of administration: Intramuscular experiment type: SINGLE co-administered:	PHENDIMETRAZINE plasma	Macaca mulatta population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
268 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23211394	1 mg/kg single, intramuscular dose: 1 mg/kg route of administration: Intramuscular experiment type: SINGLE co-administered:	PHENDIMETRAZINE plasma	Macaca mulatta population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
70 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6688092	35 mg single, oral dose: 35 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENDIMETRAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
132945 ng × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23211394	3.2 mg/kg single, intramuscular dose: 3.2 mg/kg route of administration: Intramuscular experiment type: SINGLE co-administered:	PHENDIMETRAZINE plasma	Macaca mulatta population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
15.195 ng × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23211394	0.32 mg/kg single, intramuscular dose: 0.32 mg/kg route of administration: Intramuscular experiment type: SINGLE co-administered:	PHENDIMETRAZINE plasma	Macaca mulatta population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
35.877 ng × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23211394	1 mg/kg single, intramuscular dose: 1 mg/kg route of administration: Intramuscular experiment type: SINGLE co-administered:	PHENDIMETRAZINE plasma	Macaca mulatta population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
112 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23211394	3.2 mg/kg single, intramuscular dose: 3.2 mg/kg route of administration: Intramuscular experiment type: SINGLE co-administered:	PHENDIMETRAZINE plasma	Macaca mulatta population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
114 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23211394	0.32 mg/kg single, intramuscular dose: 0.32 mg/kg route of administration: Intramuscular experiment type: SINGLE co-administered:	PHENDIMETRAZINE plasma	Macaca mulatta population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
180 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23211394	1 mg/kg single, intramuscular dose: 1 mg/kg route of administration: Intramuscular experiment type: SINGLE co-administered:	PHENDIMETRAZINE plasma	Macaca mulatta population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6688092	35 mg single, oral dose: 35 mg route of administration: Oral experiment type: SINGLE co-administered:	PHENDIMETRAZINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.7 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/018074s034lbl.pdf		PHENDIMETRAZINE unknown	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
105 mg 1 times / day steady, oral Recommended Dose: 105 mg, 1 times / day Route: oral Route: steady Dose: 105 mg, 1 times / day Co-administed with:: anorectic agents Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018074s036lbl.pdf	unhealthy Health Status: unhealthy Condition: exogenous obesity Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018074s036lbl.pdf	Disc. AE: Pulmonary hypertension... AEs leading to discontinuation/dose reduction: Pulmonary hypertension Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018074s036lbl.pdf
105 mg 1 times / day steady, oral Recommended Dose: 105 mg, 1 times / day Route: oral Route: steady Dose: 105 mg, 1 times / day Co-administed with:: dexfenfluramine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018074s036lbl.pdf	unhealthy Health Status: unhealthy Condition: exogenous obesity Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018074s036lbl.pdf	Disc. AE: Valvular heart disease NOS... AEs leading to discontinuation/dose reduction: Valvular heart disease NOS Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018074s036lbl.pdf
105 mg 1 times / day steady, oral Recommended Dose: 105 mg, 1 times / day Route: oral Route: steady Dose: 105 mg, 1 times / day Co-administed with:: fenfluramine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018074s036lbl.pdf	unhealthy Health Status: unhealthy Condition: exogenous obesity Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018074s036lbl.pdf	Disc. AE: Valvular heart disease NOS... AEs leading to discontinuation/dose reduction: Valvular heart disease NOS Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018074s036lbl.pdf

AEs

AE	Significance	Dose	Population
Pulmonary hypertension	Disc. AE	105 mg 1 times / day steady, oral Recommended Dose: 105 mg, 1 times / day Route: oral Route: steady Dose: 105 mg, 1 times / day Co-administed with:: anorectic agents Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018074s036lbl.pdf	unhealthy Health Status: unhealthy Condition: exogenous obesity Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018074s036lbl.pdf
Valvular heart disease NOS	Disc. AE	105 mg 1 times / day steady, oral Recommended Dose: 105 mg, 1 times / day Route: oral Route: steady Dose: 105 mg, 1 times / day Co-administed with:: dexfenfluramine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018074s036lbl.pdf	unhealthy Health Status: unhealthy Condition: exogenous obesity Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018074s036lbl.pdf
Valvular heart disease NOS	Disc. AE	105 mg 1 times / day steady, oral Recommended Dose: 105 mg, 1 times / day Route: oral Route: steady Dose: 105 mg, 1 times / day Co-administed with:: fenfluramine Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018074s036lbl.pdf	unhealthy Health Status: unhealthy Condition: exogenous obesity Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/018074s036lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: http://210.101.116.28/W_files/ksi3/02616057_pv.pdf Page: abstract

Sourcing

Vendor/Aggregator	ID	URL
ABI Chem	AC1L1JNO
ABI Chem	AC1L1ZN6
AHH Chemical co.,ltd	MT-57832	http://www.ahhchemical.com/product/MT-57832.html
AK Scientific	K631
Alfa Chemistry	38323-36-3	https://www.alfa-chemistry.com/cas_38323-36-3.htm
Alsachim	5010	http://www.alsachim.com/product-C6410-glo.bal-view.html
Ambinter	Amb17619240	http://www.ambinter.com/reference/17619240
BioSynth	J-501031	https://www.biosynth.com/en/products/all-products/products/J-501031.html
Bosche Scientific	D14333
ChemTik	CTK0J2878
ChemTik	CTK8I5209
Chemhere	Achem082567
Chemhere	PubCH08165
Chemieliva Pharmaceutical Co., Ltd	PBCM1237546
Chemieliva Pharmaceutical Co., Ltd	PBCM1256168
Chemieliva Pharmaceutical Co., Ltd	PBCM1366160
Clearsynth	CS-EK-01147	https://www.clearsynth.com/en/CSEK01147.html
Compound Cloud	120608
Compound Cloud	30487
Compound Cloud	6437591
Enamine	BBV-38270223
Enamine	BBV-38271027
NCI Plated 2007	108692
Norris Pharm	NSZB-A242818
NovoSeek	12460
NovoSeek	30487
Smolecule	S539387	http://www.smolecule.com/products/s539387
Smolecule	S564678	https://www.smolecule.com/products/s564678
THE BioTek	bt-279416	https://www.thebiotek.com/product/inhibitors/bt-279416
Tetrahedron	TS51343
Tetrahedron	TS83114
Toronto Research Chemicals	KIT2320
Toronto Research Chemicals	P295800
Yick-Vic Chemicals & Pharmaceuticals (HK) Ltd.	PH-1968A
ZINC	ZINC000022010387	http://zinc15.docking.org/substances/ZINC000022010387
eMolecules	252403190

PubMed

Title	Date	PubMed
Safety and tolerability of intranasal cocaine during phendimetrazine maintenance.	2016 Jun	26932737

Patents

Sample Use Guides

In Vivo Use Guide

One extended-release capsule (105 mg phendimetrazine tartrate) in the morning (30 to 60 minutes before morning meal).

Route of Administration: Oral

In Vitro Use Guide

Racemic phendimetrazine was essentially inactive at [3H]dopamine, [3H]norepinephrine, and [3H]5-HT uptake inhibition and release. The most potent effect of phendimetrazine was inhibition of [3H]norepinephrine uptake, with an IC50 of 8300 nM.

Name

Type

Language

PHENDIMETRAZINE

Official Name

English

PHENDIMETRAZINE [HSDB]

Common Name

English

Phendimetrazine [WHO-DD]

Common Name

English

NSC-169187

Code

English

PHENDIMETRAZINE [MI]

Common Name

English

PHENDIMETRAZINE [VANDF]

Common Name

English

(+)-PHENDIMETRAZINE

Common Name

English

(2S,3S)-3,4-DIMETHYL-2-PHENYLMORPHOLINE

Systematic Name

English

MORPHOLINE, 3,4-DIMETHYL-2-PHENYL-, (2S-TRANS)-

Systematic Name

English

phendimetrazine [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C29728