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Details

Stereochemistry ACHIRAL
Molecular Formula C19H21NS.ClH
Molecular Weight 331.903
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of DOTHIEPIN HYDROCHLORIDE

SMILES

Cl.CN(C)CC\C=C1/C2=C(CSC3=C1C=CC=C3)C=CC=C2

InChI

InChIKey=XUPZAARQDNSRJB-SJDTYFKWSA-N
InChI=1S/C19H21NS.ClH/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;1H/b17-11+;

HIDE SMILES / InChI

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C19H21NS
Molecular Weight 295.442
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description

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

Targets

Primary TargetPharmacologyConditionPotency
8.4 null [pKi]
18.0 nM [Kd]
109.0 nM [Kd]
38.0 nM [Kd]
61.0 nM [Kd]
92.0 nM [Kd]
8.6 nM [Kd]
46.0 nM [Kd]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Prothiaden
Primary
Prothiaden

Cmax

ValueDoseCo-administeredAnalytePopulation
27.6 ng/mL
75 mg single, oral
DOTHIEPIN plasma
Homo sapiens
9 ng/mL
25 mg single, oral
DOTHIEPIN plasma
Homo sapiens
17.7 ng/mL
25 mg single, oral
DOTHIEPIN plasma
Homo sapiens
29.49 μg/mL
50 mg single, oral
DOTHIEPIN plasma
Homo sapiens
51.1 μg/mL
100 mg single, oral
DOTHIEPIN plasma
Homo sapiens
84.95 μg/mL
150 mg single, oral
DOTHIEPIN plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
117.6 ng × h/mL
25 mg single, oral
DOTHIEPIN plasma
Homo sapiens
458.7 ng × h/mL
25 mg single, oral
DOTHIEPIN plasma
Homo sapiens
576.42 μg × h/mL
50 mg single, oral
DOTHIEPIN plasma
Homo sapiens
961.69 μg × h/mL
100 mg single, oral
DOTHIEPIN plasma
Homo sapiens
1586.14 μg × h/mL
150 mg single, oral
DOTHIEPIN plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
14.4 h
25 mg single, oral
DOTHIEPIN plasma
Homo sapiens
22 h
25 mg single, oral
DOTHIEPIN plasma
Homo sapiens
21.58 h
50 mg single, oral
DOTHIEPIN plasma
Homo sapiens
19.33 h
100 mg single, oral
DOTHIEPIN plasma
Homo sapiens
18.45 h
150 mg single, oral
DOTHIEPIN plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
5.6%
DOTHIEPIN plasma
Homo sapiens

PubMed

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
Record UNII
3H0042311V
Record Status Validated (UNII)
Record Version