U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C19H21NS
Molecular Weight 295.442
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of DOTHIEPIN

SMILES

CN(C)CC\C=C1/C2=CC=CC=C2CSC3=CC=CC=C13

InChI

InChIKey=PHTUQLWOUWZIMZ-GZTJUZNOSA-N
InChI=1S/C19H21NS/c1-20(2)13-7-11-17-16-9-4-3-8-15(16)14-21-19-12-6-5-10-18(17)19/h3-6,8-12H,7,13-14H2,1-2H3/b17-11+

HIDE SMILES / InChI
Molecular Formula C19H21NS
Molecular Weight 295.442
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/8447840 | https://www.drugs.com/uk/dosulepin-capsules-25mg-leaflet.html | https://www.ncbi.nlm.nih.gov/pubmed/9408183

cis-Dosulepin is a stereoisomer of Dothiepin (trade name Prothiaden, Dothep, Thaden, and Dopress; Dosulepin (INN, BAN) a tricyclic antidepressant that is used in several European and South Asian countries, as well as Australia, South Africa, and New Zealand. Dosulepin is used for the treatment of the major depressive disorder and neuropathic pain. Dosulepin is only Therapeutic Goods Administration and Medicines and Healthcare products Regulatory Agency approved for the treatment of the major depressive disorder. Dothiepin is not used in the United States. The central action of cis-dosulepin was compared with that of its antidepressant stereoisomer trans-dosulepin, cis-dosulepin exerted weaker anti-reserpine, anti-tetrabenazine, and 3H-5-HT (serotonin) uptake inhibiting actions than trans-dosulepin, but cis-dosulepin's inhibition of 3H-dopamine and 3H-norepinephrine uptake was slightly more potent than that of trans-dosulepin. On the other hand, cis-dosulepin exhibited extremely potent anticholinergic action in oxotremorine induced tremor, isolated ileum and the 3H-quinuclidinyl benzilate binding test. It also showed potent apomorphine enhancing the action and shortened the period of immobility in the forced swimming test in animals.

CNS Activity

Originator

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2849
 8.4 null [pKi]
Antagonist
2849
 18.0 nM [Kd]
Antagonist
2849
 109.0 nM [Kd]
Antagonist
2849
 38.0 nM [Kd]
Antagonist
2849
 61.0 nM [Kd]
Antagonist
2849
 92.0 nM [Kd]
Inhibitor
8504
 8.6 nM [Kd]
Inhibitor
8504
 46.0 nM [Kd]
Inhibitor
8504
Inhibitor
8504
Inhibitor
8504
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8583
Prothiaden

Approved Use

Unknown
Primary
Approved
8583
Prothiaden

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
27.6 ng/mL
OTHER GOV'T
https://www.info.pmda.go.jp/go/interview/2/200022_1179027F1025_2_090_1F.pdf#page=18
75 mg single, oral
dose: 75 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOTHIEPIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
9 ng/mL
OTHER GOV'T
https://www.info.pmda.go.jp/go/interview/2/200022_1179027F1025_2_090_1F.pdf#page=19 | https://pubmed.ncbi.nlm.nih.gov/6662179/
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOTHIEPIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
17.7 ng/mL
OTHER GOV'T
https://www.info.pmda.go.jp/go/interview/2/200022_1179027F1025_2_090_1F.pdf#page=19 | https://pubmed.ncbi.nlm.nih.gov/6662179/
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOTHIEPIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
29.49 μg/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/3735103/
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOTHIEPIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
51.1 μg/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/3735103/
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOTHIEPIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
84.95 μg/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/3735103/
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOTHIEPIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
117.6 ng × h/mL
OTHER GOV'T
https://www.info.pmda.go.jp/go/interview/2/200022_1179027F1025_2_090_1F.pdf#page=19 | https://pubmed.ncbi.nlm.nih.gov/6662179/
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOTHIEPIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
458.7 ng × h/mL
OTHER GOV'T
https://www.info.pmda.go.jp/go/interview/2/200022_1179027F1025_2_090_1F.pdf#page=19 | https://pubmed.ncbi.nlm.nih.gov/6662179/
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOTHIEPIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
576.42 μg × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/3735103/
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOTHIEPIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
961.69 μg × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/3735103/
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOTHIEPIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1586.14 μg × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/3735103/
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOTHIEPIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
14.4 h
OTHER GOV'T
https://www.info.pmda.go.jp/go/interview/2/200022_1179027F1025_2_090_1F.pdf#page=19 | https://pubmed.ncbi.nlm.nih.gov/6662179/
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOTHIEPIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
22 h
OTHER GOV'T
https://www.info.pmda.go.jp/go/interview/2/200022_1179027F1025_2_090_1F.pdf#page=19 | https://pubmed.ncbi.nlm.nih.gov/6662179/
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOTHIEPIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
21.58 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/3735103/
50 mg single, oral
dose: 50 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOTHIEPIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
19.33 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/3735103/
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOTHIEPIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
18.45 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/3735103/
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DOTHIEPIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
5.6%
OTHER GOV'T
https://www.info.pmda.go.jp/go/interview/2/200022_1179027F1025_2_090_1F.pdf#page=20
DOTHIEPIN plasma
Homo sapiens
PubMed

PubMed

TitleDatePubMed
Antidepressant induced cholestasis: hepatocellular redistribution of multidrug resistant protein (MRP2).
2003-02
Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding.
1999-08
Antidepressant drugs and heart electrical field.
1998
Pharmacological profile of antidepressants and related compounds at human monoamine transporters.
1997-12-11
Nightmares and hallucinations after long-term intake of tramadol combined with antidepressants.
1996
Exacerbation of extrapyramidal symptoms with paroxetine.
1995-09
Extreme suicidality following serotonin syndrome.
1995-09
Antagonism of the five cloned human muscarinic cholinergic receptors expressed in CHO-K1 cells by antidepressants and antihistaminics.
1993-06-09
[A case of choreoathetoid movements induced by anticholinergic drugs, trihexyphenidyl HCl and dosulepin HCl].
1992-09
Dothiepin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness.
1989-07
[Torsade de pointes caused by tricyclic antidepressive agents. Description of a clinical case].
1986-12
A double-blind study of the efficacy and safety of dothiepin hydrochloride in the treatment of major depressive disorder.
1984-11
A comparative study of the therapeutic effect and cardiotoxicity of dothiepin HCl and doxepin HCl in reactive depression.
1981
Patents

Patents

JP2011504928A
8
JP2011526251A
112
WO2007136743
3

Sample Use Guides

In Vivo Use Guide
male Slc:Wistar rats: 40 mg/kg, PO
Route of Administration: Oral
In Vitro Use Guide
Unknown
Substance Class Chemical
Created
by admin
on Mon Mar 31 18:16:23 GMT 2025
Edited
by admin
on Mon Mar 31 18:16:23 GMT 2025
Record UNII
W13O82Z7HL
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DOSULEPIN
EP   HSDB   INN   WHO-DD  
INN  
Preferred Name English
DOTHIEPIN
MI  
Common Name English
DOTHIRPIN
Common Name English
DOTHIEPIN [MI]
Common Name English
DOSULEPIN [EP IMPURITY]
Common Name English
dosulepin [INN]
Common Name English
Dosulepin [WHO-DD]
Common Name English
1-PROPANAMINE, 3-DIBENZO(B,E)THIEPIN-11(6H)-YLIDENE-N,N-DIMETHYL
Common Name English
(E)-3-(DIBENZO(B,E)THIEPIN-11(6H)-YLIDENE)-N,N-DIMETHYLPROPAN-1-AMINE
Systematic Name English
DOSULEPIN [HSDB]
Common Name English
Classification Tree Code System Code
WHO-VATC QN06AA16
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
NCI_THESAURUS C28197
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
WHO-ATC N06AA16
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
Code System Code Type Description
CHEBI
36798
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY
DRUG BANK
DB09167
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY
MESH
D004308
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY
CAS
113-53-1
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY
WIKIPEDIA
DOSULEPIN
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY
DRUG CENTRAL
951
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY
MERCK INDEX
m4748
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY Merck Index
IUPHAR
7549
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY
INN
1790
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY
ECHA (EC/EINECS)
204-031-2
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY
NCI_THESAURUS
C72744
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY
FDA UNII
W13O82Z7HL
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY
ChEMBL
CHEMBL1492500
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY
RXCUI
3634
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY RxNorm
PUBCHEM
5284550
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY
LACTMED
Dothiepin
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY
HSDB
7181
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY
SMS_ID
100000080788
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY
EVMPD
SUB06377MIG
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY
EPA CompTox
DTXSID2022961
Created by admin on Mon Mar 31 18:16:23 GMT 2025 , Edited by admin on Mon Mar 31 18:16:23 GMT 2025
PRIMARY
Related Record Type Details
Structure of DOTHIEPIN HYDROCHLORIDE
SALT/SOLVATE -> PARENT
Related Record Type Details
Structure of NORTHIADEN
METABOLITE ACTIVE -> PARENT
MAJOR
PLASMA
Structure of DOTHIEPIN SULFOXIDE
METABOLITE ACTIVE -> PARENT
MAJOR
PLASMA
Related Record Type Details
Structure of DOTHIEPIN
ACTIVE MOIETY
NIH
NCATS
PRIVACY NOTICE
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966