CLOCAPRAMINE DIHYDROCHLORIDE MONOHYDRATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C28H37ClN4O.2ClH.H2O
Molecular Weight	572.01
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of CLOCAPRAMINE DIHYDROCHLORIDE MONOHYDRATE

Structure Search

SMILES

O.Cl.Cl.NC(=O)C1(CCN(CCCN2C3=C(CCC4=C2C=C(Cl)C=C4)C=CC=C3)CC1)N5CCCCC5

InChI

InChIKey=SWCNPPOGIXOVAZ-UHFFFAOYSA-N

InChI=1S/C28H37ClN4O.2ClH.H2O/c29-24-12-11-23-10-9-22-7-2-3-8-25(22)33(26(23)21-24)18-6-15-31-19-13-28(14-20-31,27(30)34)32-16-4-1-5-17-32;;;/h2-3,7-8,11-12,21H,1,4-6,9-10,13-20H2,(H2,30,34);2*1H;1H2

HIDE SMILES / InChI

Description
Sources: https://medical.mt-pharma.co.jp/di/file/if/f_clo.pdf
Curator's Comment: description was created based on several sources, including: http://www.kegg.jp/medicus-bin/japic_med_product?id=00048317-003 | http://en.pharmacodia.com/web/drug/1_10640.html

Clocapramine is a chlorinated derivative of carpipramine. The hydrochloride has been given orally in the treatment of schizophrenia. Clocapramine is an antagonist of the Dopamine D2 and Serotonine (5-HT2) receptors. It has been implicated in at least one strange death, including a suicide. It augments the paroxetine in the panic disorder treatment.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Dopamine D2 receptor 311 Target ID: CHEMBL339 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7766287	Antagonist 2849	13.0 nM [Ki]
Serotonin 2a (5-HT2a) receptor 237 Target ID: CHEMBL322 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8786644	Antagonist 2849	1.9 nM [Ki]
Dopamine D3 receptor 97 Target ID: CHEMBL234 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8786644	Antagonist 2849	1.5 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Schizophrenia 305 Sources: http://www.kegg.jp/medicus-bin/japic_med_product?id=00048317-003	Primary		Approved 8583	CLOFEKTON Approved Use Clofekton 10% is indicated for the treatment of schizophrenia. Launch Date 1974

C_max

Value	Dose	Co-administered	Analyte	Population
12.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2566185/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		CLOCAPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
436 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2566185/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		CLOCAPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
46 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2566185/	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		CLOCAPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
50 mg 1 times / day multiple, oral Highest studied dose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://www.info.pmda.go.jp/go/interview/2/400315_1179030D1050_2_100_1F.pdf#page=26	unhealthy, UNKNOWN Health Status: unhealthy Age Group: UNKNOWN Sex: unknown Food Status: UNKNOWN Sources: https://www.info.pmda.go.jp/go/interview/2/400315_1179030D1050_2_100_1F.pdf#page=26	Disc. AE: Death... AEs leading to discontinuation/dose reduction: Death (grade 5) Sources: https://www.info.pmda.go.jp/go/interview/2/400315_1179030D1050_2_100_1F.pdf#page=26

AEs

AE	Significance	Dose	Population
Death	grade 5 Disc. AE	50 mg 1 times / day multiple, oral Highest studied dose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://www.info.pmda.go.jp/go/interview/2/400315_1179030D1050_2_100_1F.pdf#page=26	unhealthy, UNKNOWN Health Status: unhealthy Age Group: UNKNOWN Sex: unknown Food Status: UNKNOWN Sources: https://www.info.pmda.go.jp/go/interview/2/400315_1179030D1050_2_100_1F.pdf#page=26

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 CYP1A2 2153

Drug as perpetrator

Target	Modality	Activity
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/2793#section=Biological-Test-Results Page: 38.0	inconclusive [IC50 43.6486 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/2793#section=Biological-Test-Results Page: 38.0	inconclusive [IC50 43.6486 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/2793#section=Biological-Test-Results Page: 62.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/2793#section=Biological-Test-Results Page: 2.0	yes [IC50 2.4545 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/2793#section=Biological-Test-Results Page: 4.0	yes [IC50 4.8975 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/2793#section=Biological-Test-Results Page: 1.0

PubMed

Title	Date	PubMed
Augmentation of paroxetine with clocapramine in panic disorder.	2007-08	17610675
Atypical properties of several classes of antipsychotic drugs on the basis of differential induction of Fos-like immunoreactivity in the rat brain.	2004-11-26	15519367
Clocapramine-related fatality. Postmortem drug levels in multiple psychoactive drug poisoning.	2001-10-15	11587865
A crossover study of clocapramine and haloperidol in chronic schizophrenia.	1985	4076529

Patents

Sample Use Guides

In Vivo Use Guide

30 to 150 mg daily in three divided doses

Route of Administration: Oral

In Vitro Use Guide

Various concentrations of clocapramine was applied to NCB20 cells and reward currents were recorded. The cells were voltage-clamped at -60 mV. The compositions of internal and external solutions were both normal. Concentration-response curves for each compound were obtained from 6 to 10 cell. The Hill coefficients of clocapramine was 0.79. The Ka values for these compounds was 1.1 uM.

Name

Type

Language

CLOCAPRAMINE HYDROCHLORIDE

Preferred Name

English

CLOCAPRAMINE DIHYDROCHLORIDE MONOHYDRATE

Common Name

English

1'-(3-(3-CHLORO-10,11-DIHYDRO-5H-DIBENZ(B,F)AZEPIN-5-YL)PROPYL)(1,4'-BIPIPERIDINE)-4'-CARBOXAMIDE DIHYDROCHLORIDE MONOHYDRATE

Systematic Name

English

CLOCAPRAMINE HYDROCHLORIDE [MART.]

Common Name

English

CLOCAPRAMINE HCL

Common Name

English

Y-4153

Code

English

(1,4'-BIPIPERIDINE)-4-CARBOXAMIDE, 1'-(3-(3-CHLORO-10,11-DIHYDRO-5H-DIBENZ(B,F)AZEPIN-5-YL)PROPYL)-, HYDROCHLORIDE, HYDRATE (1:2:1)

Systematic Name

English

CLOCAPRAMINE HYDROCHLORIDE HYDRATE [JAN]

Common Name

English

CLOFEKTON

Brand Name

English

CLOCAPRAMINE DIHYDROCHLORIDE MONOHYDRATE [MI]

Common Name

English

Y 4153

Code

English

Code System Code Type Description

EVMPD

SUB01349MIG