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Details

Stereochemistry RACEMIC
Molecular Formula C11H11Cl2N.ClH
Molecular Weight 264.579
Optical Activity ( + / - )
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DOV-216303 HYDROCHLORIDE

SMILES

Cl.[H][C@]12C[C@]1(CNC2)C3=CC(Cl)=C(Cl)C=C3

InChI

InChIKey=KAGBHVBIOJBGBD-NINOIYOQSA-N
InChI=1S/C11H11Cl2N.ClH/c12-9-2-1-7(3-10(9)13)11-4-8(11)5-14-6-11;/h1-3,8,14H,4-6H2;1H/t8-,11+;/m1./s1

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C11H11Cl2N
Molecular Weight 228.118
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including http://www.siliconinvestor.com/readmsg.aspx?msgid=21695155

Amitifadine is a novel, serotonin-preferring triple reuptake inhibitor with a relative potency to inhibit serotonin (5-HT), norepinephrine (NE), and dopamine (DA) reuptake. Amitifadine is most potent against the 5-HT transporter. Amitifadine did not cause marked inhibition of major CYP450 isoenzymes, and had a good safety margin at the hERG ion channel. Initial clinical trial in patients with severe major depression demonstrated significant antidepressant activity with amitifadine, including attenuating symptoms of anhedonia, and a tolerability profile that was comparable to placebo. Amitifadine did not increase any sexual side effects as well as weight gain. It’s in phase III clinical trial for the treatment of Major depressive disorder.

Approval Year

Targets

Targets

Conditions
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
214 ng/mL
25 mg 3 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DOV-216303 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
162 ng/mL
25 mg 2 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DOV-216303 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
493 ng/mL
50 mg 2 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DOV-216303 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
712 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOV-216303 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1220 ng/mL
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOV-216303 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
191 ng/mL
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOV-216303 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
37.4 ng/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOV-216303 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2200 ng × h/mL
25 mg 3 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DOV-216303 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
902 ng × h/mL
25 mg 2 times / day multiple, oral
dose: 25 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DOV-216303 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
2460 ng × h/mL
50 mg 2 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
DOV-216303 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
3300 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOV-216303 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
5520 ng × h/mL
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOV-216303 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
911 ng × h/mL
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOV-216303 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
154 ng × h/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOV-216303 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
4 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOV-216303 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
4.4 h
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOV-216303 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
3.6 h
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOV-216303 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
3.4 h
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOV-216303 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Overview

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer






Drug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Antidepressant-like actions of DOV 21,947: a "triple" reuptake inhibitor.
2003 Feb 14
"Broad spectrum" antidepressants: is more better for the treatment of depression?
2003 Nov 7
DOV 216,303, a "triple" reuptake inhibitor: safety, tolerability, and pharmacokinetic profile.
2004 Dec
Preclinical and clinical pharmacology of DOV 216,303, a "triple" reuptake inhibitor.
2006 Summer
The novel triple reuptake inhibitor JZAD-IV-22 exhibits an antidepressant pharmacological profile without locomotor stimulant or sensitization properties.
2010 Dec
The putative antidepressant DOV 216,303, a triple reuptake inhibitor, increases monoamine release in the prefrontal cortex of olfactory bulbectomized rats.
2010 May 10
Further structure-activity relationship studies on 4-((((3S,6S)-6-benzhydryltetrahydro-2H-pyran-3-yl)amino)methyl)phenol: identification of compounds with triple uptake inhibitory activity as potential antidepressant agents.
2011 Apr 28
Synthesis and pharmacological characterization of bicyclic triple reuptake inhibitor 3-aryl octahydrocyclopenta[c]pyrrole analogues.
2011 Aug 11
Efficacy and tolerability of the novel triple reuptake inhibitor amitifadine in the treatment of patients with major depressive disorder: a randomized, double-blind, placebo-controlled trial.
2012 Jan
Biopharmaceutical characterization, metabolism, and brain penetration of the triple reuptake inhibitor amitifadine.
2013 Mar
Investigational drugs for treating major depressive disorder.
2017 Jan
Patents

Sample Use Guides

100 mg DOV 216,303 (50 mg b.i.d.)
Route of Administration: Oral
DOV 216,303 inhibits [(3)H]NE, [(3)H]5-HT, and [(3)H]DA uptake to the corresponding human recombinant transporters (expressed in HEK 293 cells) with IC(50) values of approximately 20, 14, and 78 nM, respectively. DOV 216,303 is active in tests predictive of antidepressant activity including the mouse forced swim test and reversal of tetrabenazine-induced ptosis and locomotor depression.
Substance Class Chemical
Created
by admin
on Sat Dec 16 01:27:07 GMT 2023
Edited
by admin
on Sat Dec 16 01:27:07 GMT 2023
Record UNII
06S4712H0T
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DOV-216303 HYDROCHLORIDE
Common Name English
3-AZABICYCLO(3.1.0)HEXANE, 1-(3,4-DICHLOROPHENYL)-, HYDROCHLORIDE (1:1)
Systematic Name English
3-AZABICYCLO(3.1.0)HEXANE, 1-(3,4-DICHLOROPHENYL)-, HYDROCHLORIDE (1:1), (±)-
Common Name English
(±)-AMITIFADINE HYDROCHLORIDE
Common Name English
DOV-216,303 HYDROCHLORIDE
Code English
Code System Code Type Description
PUBCHEM
11680542
Created by admin on Sat Dec 16 01:27:07 GMT 2023 , Edited by admin on Sat Dec 16 01:27:07 GMT 2023
PRIMARY
EPA CompTox
DTXSID801006647
Created by admin on Sat Dec 16 01:27:07 GMT 2023 , Edited by admin on Sat Dec 16 01:27:07 GMT 2023
PRIMARY
CAS
86215-36-3
Created by admin on Sat Dec 16 01:27:07 GMT 2023 , Edited by admin on Sat Dec 16 01:27:07 GMT 2023
NON-SPECIFIC STEREOCHEMISTRY
FDA UNII
06S4712H0T
Created by admin on Sat Dec 16 01:27:07 GMT 2023 , Edited by admin on Sat Dec 16 01:27:07 GMT 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE