Details of the Drug

General Information of Drug (ID: DMF3VXA)

Drug Name
ZOTEPINE
Synonyms
zotepine; 26615-21-4; Nipolept; Lodopin; Zoleptil; Zotepina; Zotepinum; Compound-4; Zotepina [Spanish]; Zotepinum [INN-Latin]; Zotepina [INN-Spanish]; UNII-U29O83JAZW; 2-Chloro-11-(2-(dimethylamino)ethoxy)dibenzo(b,f)thiepin; 2-Chlor-11-(2-dimethylaminoaethoxy)-dibenzo(b,f)-thiepin; C18H18ClNOS; BRN 1435710; U29O83JAZW; CHEMBL285802; CHEBI:32316; HDOZVRUNCMBHFH-UHFFFAOYSA-N; 2-[(8-chlorodibenzo[b,f]thiepin-10-yl)oxy]-N,N-dimethylethanamine; 2-Chloro-11-(2-dimethylaminoethoxy)-dibenzo(b,f)thiepine; NCGC00182081-02
Indication
Disease Entry ICD 11 Status REF
Anxiety disorder 6B00-6B0Z Approved [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 331.9
Logarithm of the Partition Coefficient (xlogp) 4.8
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 3
ADMET Property
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 6.9-19.6 mcg/L [2]
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 2-4 h [2]
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
Half-life
The concentration or amount of drug in body reduced by one-half in 21 hours [4]
Metabolism
The drug is metabolized via the CYP1A2 and CYP3A4 [5]
Vd
The volume of distribution (Vd) of drug is 109 L/kg [4]
Chemical Identifiers
Formula
C18H18ClNOS
IUPAC Name
2-(3-chlorobenzo[b][1]benzothiepin-5-yl)oxy-N,N-dimethylethanamine
Canonical SMILES
CN(C)CCOC1=CC2=CC=CC=C2SC3=C1C=C(C=C3)Cl
InChI
InChI=1S/C18H18ClNOS/c1-20(2)9-10-21-16-11-13-5-3-4-6-17(13)22-18-8-7-14(19)12-15(16)18/h3-8,11-12H,9-10H2,1-2H3
InChIKey
HDOZVRUNCMBHFH-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
5736
ChEBI ID
CHEBI:32316
CAS Number
26615-21-4
DrugBank ID
DB09225
TTD ID
D0T6QX
INTEDE ID
DR1739

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
5-HT 2A receptor (HTR2A) TTJQOD7 5HT2A_HUMAN Inhibitor [6]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [7]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Substrate [8]
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Substrate [8]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Substrate [8]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [8]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [8]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Substrate [8]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Prolactin (PRL) OTWFQGX7 PRL_HUMAN Gene/Protein Processing [9]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Anxiety disorder
ICD Disease Classification 6B00-6B0Z
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
5-HT 2A receptor (HTR2A) DTT HTR2A 1.68E-01 -0.3 -0.14
5-HT 2A receptor (HTR2A) DTT HTR2A 5.59E-01 0.15 0.21
Cytochrome P450 2B6 (CYP2B6) DME CYP2B6 9.90E-01 3.10E-03 1.75E-02
Cytochrome P450 2B6 (CYP2B6) DME CYP2B6 5.35E-01 1.10E-02 1.19E-01
Cytochrome P450 1A2 (CYP1A2) DME CYP1A2 6.73E-02 6.49E-02 3.07E-01
Cytochrome P450 1A2 (CYP1A2) DME CYP1A2 6.45E-01 2.07E-02 1.74E-01
Cytochrome P450 3A5 (CYP3A5) DME CYP3A5 1.17E-01 -3.87E-02 -2.23E-01
Cytochrome P450 3A5 (CYP3A5) DME CYP3A5 9.74E-01 7.48E-03 1.37E-01
Mephenytoin 4-hydroxylase (CYP2C19) DME CYP2C19 7.39E-01 1.54E-02 4.74E-02
Mephenytoin 4-hydroxylase (CYP2C19) DME CYP2C19 4.64E-02 -8.21E-02 -7.11E-01
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 2.59E-01 6.29E-02 3.14E-01
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 4.84E-01 -8.38E-02 -8.46E-01
Cytochrome P450 1A1 (CYP1A1) DME CYP1A1 2.32E-01 -3.66E-02 -1.30E-01
Cytochrome P450 1A1 (CYP1A1) DME CYP1A1 6.55E-01 1.27E-02 8.44E-02
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 4.66E-01 4.25E-02 1.20E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 4.75E-01 5.15E-02 3.64E-01
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 103).
2 Saletu B, Grunberger J, Anderer P, Chwatal K: [Relation between blood levels and average quantitative EEG and psychometrically assessed pharmacodynamic changes following zotepine]. Fortschr Neurol Psychiatr. 1991 Sep;59 Suppl 1:45-55. doi: 10.1055/s-2007-1000735.
3 BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
4 Single oral dose kinetics of zotepine and its relationship to prolactin response and side effects. Ther Drug Monit. 1998 Feb;20(1):117-9.
5 Zotepine monograph
6 Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501.
7 New antipsychotic agents for schizophrenia: pharmacokinetics and metabolism update. Curr Opin Investig Drugs. 2002 Jul;3(7):1073-80.
8 Identification of cytochrome P450 enzymes involved in the metabolism of zotepine, an antipsychotic drug, in human liver microsomes. Xenobiotica. 1999 Mar;29(3):217-29.
9 Differences in the effect of second-generation antipsychotics on prolactinaemia: six weeks open-label trial in female in-patients. Neuro Endocrinol Lett. 2007 Dec;28(6):881-8.