CLOMIPRAMINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H23ClN2
Molecular Weight	314.852
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(C)CCCN1C2=CC(Cl)=CC=C2CCC3=C1C=CC=C3

InChI

InChIKey=GDLIGKIOYRNHDA-UHFFFAOYSA-N

InChI=1S/C19H23ClN2/c1-21(2)12-5-13-22-18-7-4-3-6-15(18)8-9-16-10-11-17(20)14-19(16)22/h3-4,6-7,10-11,14H,5,8-9,12-13H2,1-2H3

HIDE SMILES / InChI

Molecular Formula	C19H23ClN2
Molecular Weight	314.852
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019906s039lbl.pdf

Clomipramine is an antidepressant drug which was approved by FDA for the treatment of Obsessive-Compulsive Disorder. The exact mechanism of its action is unknown, however it is supposed that it may exert its effect by inhibiting serotonin reuptake.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
serotonin uptake 20 Target ID: GO:0051610 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019906s039lbl.pdf	Inhibitor 8228

Conditions

Condition	Modality	Targets	Highest Phase	Product
Obsessive-compulsive disorder 28 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019906s039lbl.pdf	Primary		Approved 8360	ANAFRANIL Approved Use Clomipramine hydrochloride capsules USP are indicated for the treatment of obsessions and compulsions in patients with Obsessive-Compulsive Disorder (OCD). Launch Date 6.3089279E11

C_max

Value	Dose	Co-administered	Analyte	Population
31.3 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8991493	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		CLOMIPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
92 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019906s043lbl.pdf	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		CLOMIPRAMINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
736 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8991493	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		CLOMIPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
23.5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8991493	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		CLOMIPRAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED

Doses

Dose	Population	Adverse events
300 mg 1 times / day multiple, oral Recommended Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12404554/	unhealthy, 35 n = 112 Health Status: unhealthy Condition: obsessive-compulsive disorder Age Group: 35 Sex: M+F Population Size: 112 Sources: https://pubmed.ncbi.nlm.nih.gov/12404554/	Other AEs: Dry mouth, Constipation... Other AEs: Dry mouth (42.9%) Constipation (25%) Somnolence (24.1%) Tremor (22.3%) Dizziness (17.9%) Nausea (16.1%) Sweating (13.4%) Asthenia (9.8%) Insomnia (8%) Abdominal pain (3.6%) Sources: https://pubmed.ncbi.nlm.nih.gov/12404554/
200 mg 1 times / day multiple, oral (max) Recommended Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019906s043lbl.pdf	unhealthy, Children and Adolescents n = 46 Health Status: unhealthy Condition: obsessive-compulsive disorder Age Group: Children and Adolescents Sex: M+F Population Size: 46 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019906s043lbl.pdf	Other AEs: Somnolence, Tremor... Other AEs: Somnolence (46%) Tremor (33%) Dizziness (41%) Headache (28%) Insomnia (11%) Nervousness (4%) Myoclonus (2%) Paresthesia (2%) Memory impairment (7%) Anxiety (2%) Twitching (4%) Hypertonia (2%) Sleep disorder (9%) Confusion (2%) Depersonalization (2%) Irritability (2%) Panic reaction (2%) Aggressive reaction (2%) Paresis (2%) Sweating increased (9%) Rash (4%) Pruritus (2%) Skin odor abnormal (2%) Dry mouth (63%) Constipation (22%) Nausea (9%) Dyspepsia (13%) Diarrhea (7%) Anorexia (22%) Abdominal pain (13%) Vomiting (7%) Eructation (2%) Ulcerative stomatitis (2%) Fatigue (35%) Weight increase (2%) Flushing (7%) Hot flushes (2%) Chest pain (7%) Fever (2%) Allergy (7%) Pain (4%) Weight decrease (7%) Otitis media (4%) Asthenia (2%) Halitosis (2%) Postural hypotension (4%) Palpitation (4%) Tachycardia (2%) Syncope (2%) Rhinitis (7%) Sinusitis (2%) Coughing (4%) Bronchospasm (7%) Dyspnea (2%) Laryngitis (2%) Micturition disorder (4%) Urinary retention (7%) Abnormal vision (7%) Taste perversion (4%) Tinnitus (4%) Anisocoria (2%) Blepharospasm (2%) Eye allergy (2%) Disorder vestibular (2%) Muscle weakness (2%) Anemia (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019906s043lbl.pdf
250 mg 1 times / day multiple, oral (max) Recommended Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019906s043lbl.pdf	unhealthy, adult n = 322 Health Status: unhealthy Condition: obsessive-compulsive disorder Age Group: adult Sex: M+F Population Size: 322 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019906s043lbl.pdf	Other AEs: Somnolence, Tremor... Other AEs: Somnolence (54%) Tremor (54%) Dizziness (54%) Headache (52%) Insomnia (25%) Influence on libido (21%) Nervousness (18%) Myoclonus (13%) Increased appetite (11%) Paresthesia (9%) Memory impairment (9%) Anxiety (9%) Twitching (7%) Concentration impaired (5%) Depression (5%) Hypertonia (4%) Sleep disorder (4%) Psychosomatic disease (3%) Yawning (3%) Confusion (3%) Speech disorder (3%) Dreaming abnormal (3%) Agitation (3%) Migraine (3%) Depersonalization (2%) Irritability (2%) Emotional lability (2%) Panic reaction (1%) Sweating increased (29%) Rash (8%) Pruritus (6%) Dermatitis (2%) Acne (2%) Dry skin (2%) Urticaria (1%) Dry mouth (84%) Constipation (47%) Nausea (33%) Dyspepsia (22%) Diarrhea (13%) Anorexia (12%) Abdominal pain (11%) Vomiting (7%) Flatulence (6%) Tooth disorder (5%) Gastrointestinal disorder (2%) Dysphagia (2%) Esophagitis (1%) Fatigue (39%) Weight increase (18%) Flushing (8%) Hot flushes (5%) Chest pain (4%) Fever (4%) Allergy (3%) Pain (3%) Localised edema (2%) Chills (2%) Postural hypotension (6%) Palpitation (4%) Tachycardia (4%) Pharyngitis (14%) Rhinitis (12%) Sinusitis (6%) Coughing (6%) Bronchospasm (2%) Epistaxis (2%) Micturition disorder (14%) Urinary tract infection (6%) Micturition frequency (5%) Urinary retention (2%) Dysuria (2%) Cystitis (2%) Abnormal vision (18%) Taste perversion (8%) Tinnitus (6%) Lacrimation abnormal (3%) Mydriasis (2%) Conjunctivitis (1%) Myalgia (13%) Back pain (6%) Arthralgia (3%) Muscle weakness (1%) Purpura (3%) Thirst (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/019906s043lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1709	substrate 1010	substrate 1193	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1437 OCT1 506	CYP1A1 348 CYP1A2 1032 CYP2C8 688 CYP2C18 139 CYP2C19 985 UGT2B10 127 UGT1A4 347

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
OCT1 523	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/18788725/	yes
P-gp 1626	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/21718296/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
UGT2B10 127	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/20133892/	major
UGT1A4 347	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/20133892/	minor
CYP1A1 348	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/	no
CYP2C18 139	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/	no
CYP2C8 688	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/	no
CYP2C9 1010	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/	no
CYP1A2 1032	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/	yes
CYP3A4 1709	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/	yes
CYP2C19 985	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/ \| https://pubmed.ncbi.nlm.nih.gov/28470111/	yes	yes (pharmacogenomic study) Comment: administration of clomipramine to a CYP2C19 intermediate metabolizer resulted in elevated serum trough concentrations Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/ \| https://pubmed.ncbi.nlm.nih.gov/28470111/
CYP2D6 1193	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/ \| https://pubmed.ncbi.nlm.nih.gov/20531370/ \| https://pubmed.ncbi.nlm.nih.gov/28470111/	yes	yes (pharmacogenomic study) Comment: administration of clomipramine to a CYP2D6 intermediate metabolizer resulted in elevated serum trough concentrations Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/ \| https://pubmed.ncbi.nlm.nih.gov/20531370/ \| https://pubmed.ncbi.nlm.nih.gov/28470111/

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1632	inhibitor 1613 Sources: https://pubmed.ncbi.nlm.nih.gov/18634780/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:47780	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:47780
ChemicalBook	CB5173107	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5173107
MolPort	MolPort-002-051-949	https://www.molport.com/shop/molecule-link/MolPort-002-051-949
MolPort	MolPort-047-115-334	https://www.molport.com/shop/molecule-link/MolPort-047-115-334
ZINC	ZINC000000020248	http://zinc15.docking.org/substances/ZINC000000020248
eMolecules	1883437	https://www.emolecules.com/cgi-bin/more?vid=1883437

PubMed

Title	Date	PubMed
Obstructive sleep apnea syndrome induced by clonazepam in a narcoleptic patient with REM-sleep-behavior disorder.	1999 Dec	10646174
[The influence of clomipramine-induced mania on rapid cycling affective disorder].	1999 Dec 1	10629901
A puzzling case of seizures and visual hallucinations during clomipramine treatment with a high dose but causing a low serum concentration.	1999 May	10353456
Side effects as predictors of drug response in obsessive-compulsive disorder.	1999 Oct	10505588
Seizures caused by possible interaction between olanzapine and clomipramine.	2000 Apr	10770480
Long-term effects of tricyclic antidepressants on norepinephrine kinetics in humans.	2001	11341486
Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction.	2001	11229449
Development of a depersonalization severity scale.	2001 Apr	11469161
Clomipramine versus haloperidol in the treatment of autistic disorder: a double-blind, placebo-controlled, crossover study.	2001 Aug	11476129
S33005, a novel ligand at both serotonin and norepinephrine transporters: II. Behavioral profile in comparison with venlafaxine, reboxetine, citalopram, and clomipramine.	2001 Aug	11454919
S33005, a novel ligand at both serotonin and norepinephrine transporters: I. Receptor binding, electrophysiological, and neurochemical profile in comparison with venlafaxine, reboxetine, citalopram, and clomipramine.	2001 Aug	11454918
A review of the pharmacological and clinical profile of mirtazapine.	2001 Fall	11607047
Severe, refractory hypotension during anesthesia in a patient on chronic clomipramine therapy.	2001 Jul	11465569
The critical window of brain development from susceptive to insusceptive. Effects of clomipramine neonatal treatment on sexual behavior.	2001 Jul 23	11454417
Comparison of peripheral inhibitory effects of clomipramine with selective serotonin re-uptake inhibitors on contraction of vas deferens: in vitro and in vivo studies.	2001 Jun	11371937
Cortical 5-HT(1A) receptor downregulation by antidepressants in rat brain.	2001 Jun	11290382
Pharmacological treatment of childhood obsessive-compulsive disorder: from theory to practice.	2001 Mar	11294079
A dose-finding and discontinuation study of clomipramine in panic disorder.	2001 Mar	11277602
Effective daily treatment with clomipramine in men with premature ejaculation when 25 mg (as required) is ineffective.	2001 Mar	11251530
[A classic antidepressant as an analgesic. Chronic pain under secure control].	2001 May 28	11434267
Adults with early-onset obsessive-compulsive disorder.	2001 Nov	11691698
Antidepressant drug treatments induce glial cell line-derived neurotrophic factor (GDNF) synthesis and release in rat C6 glioblastoma cells.	2001 Oct	11595754
Spontaneous reports on drug-induced pancreatitis in Denmark from 1968 to 1999.	2001 Sep	11699619
Effectiveness of pharmacotherapy for body dysmorphic disorder: a chart-review study.	2001 Sep	11681769
High-performance liquid chromatographic method to screen and quantitate seven selective serotonin reuptake inhibitors in human serum.	2001 Sep 25	11587344

Patents

Sample Use Guides

In Vivo Use Guide

Adults: Treatment should be initiated at a dosage of 25 mg daily and gradually increased, as tolerated, to approximately 100 mg during the first 2 weeks. During initial titration, the drug should be given in divided doses with meals to reduce gastrointestinal side effects. Thereafter, the dosage may be increased gradually over the next several weeks, up to a maximum of 250 mg daily.

Route of Administration: Oral

In Vitro Use Guide

The effect of clomipramine, at concentrations of 10(-7)M to 10(-4)M, was studied in vitro on the uptake of 5-hydroxytryptamine and dopamine uptake in human platelet-rich plasma.

Substance Class	Chemical Created by `admin` on `Wed Jul 05 22:31:49 UTC 2023` Edited by `admin` on `Wed Jul 05 22:31:49 UTC 2023`
Record UNII	NUV44L116D
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CLOMIPRAMINE

Official Name

English

Clomipramine [WHO-DD]

Common Name

English

NSC-169865

Code

English

CHLORIMIPRAMINE

Common Name

English

CLOMIPRAMINE [MI]

Common Name

English

ANAPRAMINE

Common Name

English

clomipramine [INN]

Common Name

English

3-CHLORO-5-(3-(DIMETHYLAMINO)PROPYL)-10,11-DIHYDRO-5H-DIBENZ(B,F)AZEPINE

Systematic Name

English

5H-DIBENZ(B,F)AZEPINE-5-PROPANAMINE, 3-CHLORO-10,11-DIHYDRO-N,N-DIMETHYL-

Systematic Name

English

CLOMICALM

Brand Name

English

3-CHLORO-IMINODIBENZYL

Common Name

English

CLOMIPRAMINE [HSDB]

Common Name

English

CLOMIPRAMINE [VANDF]

Common Name

English

CLOMIPRAMINE [EMA EPAR VETERINARY]

Common Name

English

Classification Tree Code System Code

WHO-ESSENTIAL MEDICINES LIST

24.4