CLOMIPRAMINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H23ClN2
Molecular Weight	314.853
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(C)CCCN1c2ccccc2CCc3ccc(cc31)Cl

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	314.853
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 19 Target ID: GO:0051610 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019906s039lbl.pdf	Inhibitor 7728

Conditions

Condition	Modality	Targets	Highest Phase	Product
Obsessive-compulsive disorder 26 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019906s039lbl.pdf	Primary		Approved 8043	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 1601	substrate 936	substrate 1118	inhibitor 1475

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1330 OCT1 480	CYP1A1 325 CYP1A2 972 CYP2C8 634 CYP2C18 135 CYP2C19 910 UGT2B10 125 UGT1A4 330

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
OCT1 495	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/18788725/	yes
P-gp 1514	inhibitor 3045 Sources: https://pubmed.ncbi.nlm.nih.gov/21718296/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
UGT2B10 125	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/20133892/	major
UGT1A4 330	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/20133892/	minor
CYP1A1 325	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/	no
CYP2C18 135	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/	no
CYP2C8 634	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/	no
CYP2C9 936	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/	no
CYP1A2 972	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/	yes
CYP3A4 1601	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/	yes
CYP2C19 910	substrate 3113 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 1118	substrate 3113 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 1507	inhibitor 1489 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
Letter: Clonazepam in the treatment of drug-induced dyskinesia.	1975 Feb 1	1111773
[The influence of clomipramine-induced mania on rapid cycling affective disorder].	1999 Dec 1	10629901
[Neuropsychiatric symptoms in preventive antimalarial treatment with mefloquine: apropos of 2 cases].	2000 Jul-Aug	11064842
Serotonin and dopamine antagonism in obsessive-compulsive disorder: effect of atypical antipsychotic drugs.	2000 Nov	11147933
Availability of learned helplessness test as a model of depression compared to a forced swimming test in rats.	2001	11598420
Psychogenic excoriation. Clinical features, proposed diagnostic criteria, epidemiology and approaches to treatment.	2001	11475941
Involvement of potassium channels in amitriptyline and clomipramine analgesia.	2001	11077073
Simultaneous analysis of clozapine, clomipramine and their metabolites by reversed-phase liquid chromatography.	2001 Apr	11370995
Reactivity of serotonin in whole blood: relationship with drug response in obsessive-compulsive disorder.	2001 Feb 15	11239907
Antidepressants alter cell proliferation in the adult brain in vivo and in neural cultures in vitro.	2001 Jan 5	11137860
A single blind comparison of amisulpride, fluoxetine and clomipramine in the treatment of restricting anorectics.	2001 Jul	11444677
Neurobiology and clinical pharmacology of obsessive-compulsive disorder.	2001 Jul-Aug	11479390
Synthesis and antidepressant activities of some 3,5-diphenyl-2-pyrazolines.	2001 Jun	11525844
Diurnal profile of melatonin concentrations in patients with major depression: relationship to the clinical manifestation and antidepressant treatment.	2001 Jun	11449197
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
Pharmacological treatment of childhood obsessive-compulsive disorder: from theory to practice.	2001 Mar	11294079
Effective daily treatment with clomipramine in men with premature ejaculation when 25 mg (as required) is ineffective.	2001 Mar	11251530
Long-term effects of clomipramine and fluoxetine on dorsal periaqueductal grey-evoked innate defensive behaviours of the rat.	2001 May	11432688
A meta-analysis of the efficacy and tolerability of paroxetine versus tricyclic antidepressants in the treatment of major depression.	2001 May	11354239
[A classic antidepressant as an analgesic. Chronic pain under secure control].	2001 May 28	11434267
Antidepressant drug treatments induce glial cell line-derived neurotrophic factor (GDNF) synthesis and release in rat C6 glioblastoma cells.	2001 Oct	11595754
Clinical predictors of drug response in obsessive-compulsive disorder.	2001 Oct	11593074
Taijin kyofusho: a form of social anxiety disorder that responds to serotonin reuptake inhibitors?	2001 Sep	11602029
Comment: serotonin syndrome and 5-HT2A antagonism.	2001 Sep	11573872
Differential time-course profiles of dopamine release and uptake changes induced by three dopamine uptake inhibitors.	2001 Sep 15	11494401
High-performance liquid chromatographic method to screen and quantitate seven selective serotonin reuptake inhibitors in human serum.	2001 Sep 25	11587344
Diurnal profile of melatonin secretion in the acute phase of major depression and in remission.	2001 Sep-Oct	11535940

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 `Sat Jun 26 12:54:46 UTC 2021` Edited by `admin` on `Sat Jun 26 12:54:46 UTC 2021`
Record UNII	NUV44L116D
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CLOMIPRAMINE

Official Name

English

NSC-169865

Code

English

CHLORIMIPRAMINE

Common Name

English

CLOMIPRAMINE [MI]

Common Name

English

ANAPRAMINE

Common Name

English

CLOMIPRAMINE [WHO-DD]

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