FENFLURAMINE

First approved in 1973

Details

Stereochemistry	RACEMIC
Molecular Formula	C12H16F3N
Molecular Weight	231.2573
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCNC(C)CC1=CC(=CC=C1)C(F)(F)F

InChI

InChIKey=DBGIVFWFUFKIQN-UHFFFAOYSA-N

InChI=1S/C12H16F3N/c1-3-16-9(2)7-10-5-4-6-11(8-10)12(13,14)15/h4-6,8-9,16H,3,7H2,1-2H3

HIDE SMILES / InChI

Molecular Formula	C12H16F3N
Molecular Weight	231.2573
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: https://www.drugbank.ca/drugs/DB00574
Curator's Comment: description was created based on several sources, including https://www.drugs.com/international/fenfluramine.html | https://www.ncbi.nlm.nih.gov/pubmed/24790728 | https://clinicaltrials.gov/ct2/show/NCT02655198 | https://www.ncbi.nlm.nih.gov/pubmed/27264138 | https://www.ncbi.nlm.nih.gov/pubmed/22554283 | https://www.ncbi.nlm.nih.gov/pubmed/26600876

Fenfluramine (former brand names Pondimin, Ponderax and Adifax), also known as 3-trifluoromethyl-N-ethylamphetamine, is an anorectic that is no longer marketed. In combination with phentermine, it was part of the anti-obesity medication Fen-phen. Fenfluramine was introduced on the U.S. market in 1973 and withdrawn in 1997. It is the racemic mixture of two enantiomers, dexfenfluramine, and levofenfluramine. The drug increases the level of serotonin, a neurotransmitter that regulates mood, appetite and other functions. Fenfluramine causes the release of serotonin by disrupting vesicular storage of the neurotransmitter and reversing serotonin transporter function. The drug was withdrawn from the U.S. market in 1997 after reports of heart valve disease and pulmonary hypertension, including a condition known as cardiac fibrosis. It was subsequently withdrawn from other markets around the world. In this small exploratory and retrospective study, remarkably good results were reported on the use of fenfluramine as an add-on medication for controlling seizures in patients with the Dravet syndrome. The side effects were rare and nonserious and did not result in termination of the treatment. It is possible that this drug may have anticonvulsive effects for other severe epilepsy syndromes, especially in those characterized by photosensitive or induced seizures.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
serotonin secretion 8 Target ID: GO:0001820 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16237679	Activator 1410

Conditions

Condition	Modality	Highest Phase	Product
Obesity 204 Sources: http://www.rxlist.com/pondimin-drug/indications-dosage.htm	Primary	Approved 8360	Pondimin Approved Use Unknown
Epilepsy 122 Sources: https://clinicaltrials.gov/ct2/show/NCT02655198	Primary	Phase II 1144	Pondimin Approved Use Unknown
Lennox gastaut syndrome 2 Sources: https://clinicaltrials.gov/ct2/show/NCT02655198	Primary	Phase II 1144	Pondimin Approved Use Unknown
Dravet syndrome 5 Sources: https://clinicaltrials.gov/ct2/show/NCT02682927	Primary	Phase III 663	Pondimin Approved Use Unknown
Seizure disorders 4 Sources: https://clinicaltrials.gov/ct2/show/NCT02682927	Primary	Phase III 663	Pondimin Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
68 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212102s000lbl.pdf	0.35 mg/kg 2 times / day steady-state, oral dose: 0.35 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:		FENFLURAMINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1390 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212102s000lbl.pdf	0.35 mg/kg 2 times / day steady-state, oral dose: 0.35 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:		FENFLURAMINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
20 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212102s000lbl.pdf	0.35 mg/kg 2 times / day steady-state, oral dose: 0.35 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:		FENFLURAMINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
50% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212102s000lbl.pdf	0.35 mg/kg 2 times / day steady-state, oral dose: 0.35 mg/kg route of administration: Oral experiment type: STEADY-STATE co-administered:		FENFLURAMINE plasma	Homo sapiens population: UNHEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
60 mg/day 1 times / day steady, oral Highest studied dose Dose: 60 mg/day, 1 times / day Route: oral Route: steady Dose: 60 mg/day, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3134879/	unhealthy, 11 years n = 1 Health Status: unhealthy Condition: Valsalva's maneuver Age Group: 11 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/3134879/	Sources: https://pubmed.ncbi.nlm.nih.gov/3134879/
0.2 mg/kg/day 2 times / day steady, oral Studied dose Dose: 0.2 mg/kg/day, 2 times / day Route: oral Route: steady Dose: 0.2 mg/kg/day, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30146701	unhealthy, 11.7 ± 4.4 years (range: 3‐17 years) n = 13 Health Status: unhealthy Condition: Lennox‐Gastaut syndrome (LGS) Age Group: 11.7 ± 4.4 years (range: 3‐17 years) Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/30146701	Other AEs: Decreased appetite... Other AEs: Decreased appetite (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/30146701
0.7 mg/kg/day 1 times / day steady, oral Studied dose Dose: 0.7 mg/kg/day, 1 times / day Route: oral Route: steady Dose: 0.7 mg/kg/day, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212102s000lbl.pdf	unhealthy n = 40 Health Status: unhealthy Sex: unknown Population Size: 40 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212102s000lbl.pdf	Disc. AE: Somnolence... AEs leading to discontinuation/dose reduction: Somnolence (3.3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212102s000lbl.pdf

AEs

AE	Significance	Dose	Population
Decreased appetite	2 patients	0.2 mg/kg/day 2 times / day steady, oral Studied dose Dose: 0.2 mg/kg/day, 2 times / day Route: oral Route: steady Dose: 0.2 mg/kg/day, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30146701	unhealthy, 11.7 ± 4.4 years (range: 3‐17 years) n = 13 Health Status: unhealthy Condition: Lennox‐Gastaut syndrome (LGS) Age Group: 11.7 ± 4.4 years (range: 3‐17 years) Sex: M+F Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/30146701
Somnolence	3.3% Disc. AE	0.7 mg/kg/day 1 times / day steady, oral Studied dose Dose: 0.7 mg/kg/day, 1 times / day Route: oral Route: steady Dose: 0.7 mg/kg/day, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212102s000lbl.pdf	unhealthy n = 40 Health Status: unhealthy Sex: unknown Population Size: 40 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212102s000lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1579 inducer 768	substrate 1010 inhibitor 1752 inducer 383	substrate 1193 inhibitor 1837 inducer 97

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1509 CYP2B6 799 CYP2C8 901 CYP2C19 1463 P-gp 1437 BCRP 691 OATP1B1 781 OATP1B3 700 OAT1 595 OAT3 636 OCT2 638 MATE1 304 MATE2 261	CYP1A2 1032 CYP2B6 660 CYP2C19 985 CYP3A4/5 85 OAT3 333 OCT2 348 MATE1 132 MATE2 94 BCRP 555 OAT1 320	CYP1A2 689 CYP2B6 538 CYP2C8 168 CYP2C19 290

Drug as perpetrator

Target	Modality	Activity	Metabolite
BCRP 765	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
BCRP 765	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
CYP1A2 1673	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
CYP2B6 985	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP2B6 985	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP2B6 985	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
CYP2C19 1537	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
CYP2C8 955	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP2C8 955	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP2C8 955	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
CYP2C9 1803	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
CYP2D6 1875	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP2D6 1875	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP2D6 1875	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
CYP3A4 1909	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP3A4 1909	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
CYP3A4 1909	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
MATE1 306	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
MATE1 306	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
MATE2 261	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
MATE2 261	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
OAT1 599	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
OAT1 599	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
OAT3 638	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
OAT3 638	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
OATP1B1 796	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
OATP1B1 796	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
OATP1B3 709	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
OATP1B3 709	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
OCT2 639	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
OCT2 639	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
P-gp 1626	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
P-gp 1626	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2C9 1010	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	minor
CYP2C19 985	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	minor		unlikely (co-administration study) Comment: The effect of coadministration of CBD on fenfluramine and norfenfluramine PK was evaluated in Study 1604. The study demonstrated that co-administration of CBD with ZX008 increased fenfluramine AUC0-t by approximately 59% and the Cmax was not changed significantly. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0
CYP3A4/5 85	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	minor		unlikely (co-administration study) Comment: The effect of coadministration of CBD on fenfluramine and norfenfluramine PK was evaluated in Study 1604. The study demonstrated that co-administration of CBD with ZX008 increased fenfluramine AUC0-t by approximately 59% and the Cmax was not changed significantly. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0
BCRP 555	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
BCRP 555	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
MATE1 132	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
MATE1 132	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
MATE2 94	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
MATE2 94	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
OAT1 320	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
OAT1 320	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
OAT3 333	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
OAT3 333	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
OCT2 348	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no
OCT2 348	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	no	NORFENFLURAMINE 2
CYP2D6 1193	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	yes
CYP1A2 1032	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	yes		unlikely (co-administration study) Comment: The effect of coadministration of CBD on fenfluramine and norfenfluramine PK was evaluated in Study 1604. The study demonstrated that co-administration of CBD with ZX008 increased fenfluramine AUC0-t by approximately 59% and the Cmax was not changed significantly. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0
CYP2B6 660	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0	yes		unlikely (co-administration study) Comment: The effect of coadministration of CBD on fenfluramine and norfenfluramine PK was evaluated in Study 1604. The study demonstrated that co-administration of CBD with ZX008 increased fenfluramine AUC0-t by approximately 59% and the Cmax was not changed significantly. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000ClinPharmR.pdf#page=6 Page: 6.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
Nav1.5 98	binder 5 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2020/212102Orig1s000OtherR.pdf#page=38 Page: 38.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:59729	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:59729
eMolecules	538306	https://www.emolecules.com/cgi-bin/more?vid=538306

PubMed

Title	Date	PubMed
Treatment of obesity with fenfluramine.	1975 Jan 31	1124579
The effect of cold and diazepam on the toxicity of fenfluramine in mice.	1975 Mar 15	1116545
Appetite-suppressing drugs and valvular heart disease.	1999 Nov-Dec	11208248
[Obesity: principles of drug therapy].	2000 Aug	11026090
[Valvular regurgitation caused by anorectic agents].	2000 Dec	11171493
Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications.	2000 Dec 5	11104741
Understanding the neurobiology of suicidal behavior.	2001	11747126
Neuroendocrine responses to fenfluramine and its relationship to personality in alcoholism.	2001	11716144
Neurotransmitter and hormonal background of hostility in anorexia nervosa.	2001	11340360
Comparison of [(18)F]altanserin and [(18)F]deuteroaltanserin for PET imaging of serotonin(2A) receptors in baboon brain: pharmacological studies.	2001 Apr	11323237
Anorectic drugs and pulmonary hypertension from the bedside to the bench.	2001 Apr	11307870
Appetite suppressants and valvular heart disease.	2001 Apr	11307869
Cataleptic effect of neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one in mice: modulation by serotonergic agents.	2001 Apr 13	11292445
Association between selective serotonin-reuptake inhibitor therapy and heart valve regurgitation.	2001 Apr 15	11305992
Neuroendocrine serotonergic and dopaminergic responsivity in male schizophrenic patients during treatment with neuroleptics and after switch to risperidone.	2001 Aug	11512043
Fenfluramine-induced pulmonary vasoconstriction: role of serotonin receptors and potassium channels.	2001 Aug	11457791
Cholesterol and serotonin indices in depressed and suicidal patients.	2001 Feb	11223109
Elevations in plasmatic titers of corticosterone and aldosterone, in the absence of changes in ACTH, testosterone, or glial fibrillary acidic protein, 72 h following D,L-fenfluramine or D-fenfluramine administration to rats.	2001 Jan-Feb	11274873
Low risk of significant echocardiographic valvulopathy in patients treated with anorectic drugs.	2001 Jul	11461737
Lack of effect of HPA axis hyperactivity on hormonal responses to d-fenfluramine in major depressed patients: implications for pathogenesis of suicidal behaviour.	2001 Jul	11337135
Prolactin response to d-fenfluramine in postmenopausal women on and off ERT: comparison with young women.	2001 Jul	11337133
3,4-Methylenedioxymethamphetamine (MDMA) as a unique model of serotonin receptor function and serotonin-dopamine interactions.	2001 Jun	11356903
Transcranial magnetic stimulation and antidepressive drugs share similar cellular effects in rat hippocampus.	2001 Jun	11331140
Echocardiographic examination of women previously treated with fenfluramine: long-term follow-up of a randomized, double-blind, placebo-controlled trial.	2001 Jun 11	11386892
Bitter pills, bad medicine.	2001 Jun 4	11432381
In vitro reaction of formaldehyde with fenfluramine: conversion to N-methyl fenfluramine.	2001 Mar	11300512
Medial versus lateral parabrachial nucleus lesions in the rat: effects on cholecystokinin- and D-fenfluramine-induced anorexia.	2001 Mar 16	11251203
By the way, doctor...I used a diet pill--fenfluramine--a few years ago, but stopped as soon as I heard about it causing heart-valve problems. My doctor has been doing echocardiograms on me every six months. So far, everything looks good. How long do you think I need to keep on getting these checkups?	2001 May	11424276
Rapid clot formation and abnormal fibrin structure in a symptomatic patient taking fenfluramine--a case report.	2001 May	11386389
Decreased tryptophan availability but normal post-synaptic 5-HT2c receptor sensitivity in chronic fatigue syndrome.	2001 May	11352361
Too late, again?	2001 May-Jun	11420587
Effects of endogenous neurotransmitters on the in vivo binding of dopamine and 5-HT radiotracers in mice.	2001 Nov	11682251
LY393558, a 5-hydroxytryptamine reuptake inhibitor and 5-HT(1B/1D) receptor antagonist: effects on extracellular levels of 5-hydroxytryptamine in the guinea pig and rat.	2001 Nov 30	11734183
MDMA and fenfluramine alter the response of the circadian clock to a serotonin agonist in vitro.	2001 Nov 30	11716826
Fluorometric determination of DL-fenfluramine, DL-norfenfluramine and phentermine in plasma by achiral and chiral high-performance liquid chromatography.	2001 Nov 5	11710586
Fenfluramine and phentermine.	2001 Nov 6	11694113
Monoamine oxidase inhibition is unlikely to be relevant to the risks associated with phentermine and fenfluramine: a comparison with their abilities to evoke monoamine release.	2001 Oct	11673765
Operation for anorexigen-associated valvular heart disease.	2001 Oct	11581595
High performance liquid chromatography with UV detection for the simultaneous determination of sympathomimetic amines using 4-(4,5-diphenyl-1H-imidazole-2-yl)benzoyl chloride as a label.	2001 Oct	11559922
Clinical and echocardiographic follow-up of patients previously treated with dexfenfluramine or phentermine/fenfluramine.	2001 Oct 24-31	11667938
Acute effects of D-fenfluramine on simultaneous measures of aggressive escape and impulsive responses of adult males with and without a history of conduct disorder.	2001 Sep	11605076
Acute anorectic effect of single and combined drugs in mice using a non-deprivation protocol.	2001 Sep	11594445
Risk factors for pulmonary arterial hypertension.	2001 Sep	11590841
Prolactin response to dl-fenfluramine challenge before and after treatment with paroxetine.	2001 Sep	11522467
Neuroendocrine effects of d-fenfluramine and bromocriptine following repeated smoked cocaine in humans.	2001 Sep 1	11470342
Anorexigen-induced pulmonary hypertension and the serotonin (5-HT) hypothesis: lessons for the future in pathogenesis.	2002	11806844
Retest reliability of prolactin response to dl-fenfluramine challenge in adults.	2002 Feb	11790522
Pharmacological studies of the acute effects of (+)-3,4-methylenedioxymethamphetamine on locomotor activity: role of 5-HT(1B/1D) and 5-HT(2) receptors.	2002 Jan	11751031
Is long-term heavy alcohol consumption toxic for brain serotonergic neurons? Relationship between years of excessive alcohol consumption and serotonergic neurotransmission.	2002 Jan 1	11772477
Inhibition of cocaine self-administration by fluoxetine or D-fenfluramine combined with phentermine.	2002 Jan-Feb	11812523

Patents

Sample Use Guides

In Vivo Use Guide

0.12–0.90 mg/kg/day

Route of Administration: Oral

In Vitro Use Guide

Rat midbrain slices were used to make intracellular recordings from dopaminergic neurons of the substantia nigra and the ventral tegmental area. Gamma-aminobutyric acid (GABA)-mediated synaptic transmission was assessed from the inhibitory postsynaptic potentials (IPSPs) mediated by GABAA and GABAB receptors. Intracellular recordings from midbrain SNpc and VTA dopaminergic neurons were performed at 33.0 +/- 0.5°C in a recording chamber submerged with aCSF flowing at a rate of 2.5–3 mL•min-1 and continuously oxygenated, on the stage of an upright (inverted) microscope (Axioscope FS, Zeiss, Gottingen, Germany), equipped for infrared video microscopy (Hamamatsu, Tokyo, Japan) in order to allow a direct visualization of the recorded cells. Neurons, selected for their morphology, were identified as dopaminergic by their electrophysiological properties such as the presence of a regular spontaneous firing activity (0.5–4 Hz), a large inward current (Ih) in response to hyperpolarizing voltages and a membrane hyperpolarization due to dopamine (10–30 mmol•L-1) application . The recording electrodes were filled with 2 mol•L-1 KCl and had a tip resistance of 30–80 MW. GABAB synaptic potentials were evoked using a bipolar tungsten stimulating electrode with a tip separation of 300–700 mkm. Representative recordings showing the effect of fenfluramine in reducing the GABAB-mediated IPSP. Such effects were evident at concentrations below 1 mmol•L-1. The amplitude of synaptic potentials was halved by fenfluramine at concentration around 10 mmol•L-1 and was completely blocked by CGP (1 mmol•L-1), a selective GABAB receptor antagonist. Fenfluramine and sibutramine induce a concentration-dependent reduction of the GABAB-mediated inhibitory postsynaptic potentials (IPSPs).

Substance Class	Chemical Created by `admin` on `Wed Jul 05 22:41:45 UTC 2023` Edited by `admin` on `Wed Jul 05 22:41:45 UTC 2023`
Record UNII	2DS058H2CF
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FENFLURAMINE

Official Name

English

PONDERAX

Brand Name

English

S-768

Code

English

2-ETHYLAMINO-1-(3-TRIFLUOROMETHYLPHENYL)PROPANE

Systematic Name

English

PONDERAX PA

Common Name

English

FENFLURAMINE [VANDF]

Common Name

English

FENFLURAMINE [MI]

Common Name

English

BRABAFEN

Brand Name

English

N-ETHYL-.ALPHA.-METHYL-3-(TRIFLUOROMETHYL)BENZENEETHANAMINE

Systematic Name

English

N-ETHYL-.ALPHA.-METHYL-M-(TRIFLUOROMETHYL)PHENETHYLAMINE

Systematic Name

English

Z008

Code

English

BENZENEETHANAMINE, N-ETHYL-.ALPHA.-METHYL-3-(TRIFLUOROMETHYL)-

Systematic Name

English

Z-008

Code

English

OBEDREX

Common Name

English

fenfluramine [INN]

Common Name

English

PHENFLURAMINE

Common Name

English

PESOS

Common Name

English

ROTONDIN

Common Name

English

J5.760F

Code

English

FENFLURAMIN

Common Name

English

ACINO

Common Name

English

ZX008

Code

English

FENFLURAMINE [HSDB]

Common Name

English

ZX-008

Code

English

Fenfluramine [WHO-DD]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

584217