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
Depressive reactions in the course of clomipramine therapy used in the treatment of obsessional conditions.	1975	1154013
Pharmacotherapy for severe aggression in a child with autism: "open label" evaluation of multiple medications on response frequency and intensity of behavioral intervention.	2000 Sep-Dec	11494958
Trichotillomania. Presentation, etiology, diagnosis and therapy.	2001	11721651
Availability of learned helplessness test as a model of depression compared to a forced swimming test in rats.	2001	11598420
Vasopressin-dependent flank marking in golden hamsters is suppressed by drugs used in the treatment of obsessive-compulsive disorder.	2001	11545675
Smoking in patients receiving psychotropic medications: a pharmacokinetic perspective.	2001	11524025
Pharmacological characterization of the serotonin transporter in young and elderly subjects.	2001	11490175
Psychogenic excoriation. Clinical features, proposed diagnostic criteria, epidemiology and approaches to treatment.	2001	11475941
Tianeptine: a review of its use in depressive disorders.	2001	11463130
Development of a depersonalization severity scale.	2001 Apr	11469161
Interaction of psychotropic drugs with monoamine oxidase in rat brain.	2001 Aug	11518022
Neuroendocrine serotonergic and dopaminergic responsivity in male schizophrenic patients during treatment with neuroleptics and after switch to risperidone.	2001 Aug	11512043
Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients.	2001 Aug	11477329
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
Altered dendritic spine density in animal models of depression and in response to antidepressant treatment.	2001 Dec 1	11746712
A review of the pharmacological and clinical profile of mirtazapine.	2001 Fall	11607047
Long-term follow-up and predictors of clinical outcome in obsessive-compulsive patients treated with serotonin reuptake inhibitors and behavioral therapy.	2001 Jul	11488364
Severe, refractory hypotension during anesthesia in a patient on chronic clomipramine therapy.	2001 Jul	11465569
A single blind comparison of amisulpride, fluoxetine and clomipramine in the treatment of restricting anorectics.	2001 Jul	11444677
The critical window of brain development from susceptive to insusceptive. Effects of clomipramine neonatal treatment on sexual behavior.	2001 Jul 23	11454417
[Tricyclic antidepressants dosage and depressed elderly inpatients: a retrospective pharmaco-epidemiologic study].	2001 Jul-Aug	11686060
Digitalis intoxication misdiagnosed as depression--revisited.	2001 Jul-Aug	11496033
Neurobiology and clinical pharmacology of obsessive-compulsive disorder.	2001 Jul-Aug	11479390
Clomipramine--beyond separation anxiety.	2001 Jul-Aug	11450830
Synthesis and antidepressant activities of some 3,5-diphenyl-2-pyrazolines.	2001 Jun	11525844
Pharmacological manipulations of the extinction process of fear-induced ultrasonic vocalization in rats.	2001 Jun	11459003
Diurnal profile of melatonin concentrations in patients with major depression: relationship to the clinical manifestation and antidepressant treatment.	2001 Jun	11449197
[Value of fluoxetine in obsessive-compulsive disorder in the adult: review of the literature].	2001 May-Jun	11488259
[Narcolepsy in a prepubertal boy].	2001 Nov	11725521
Antidepressants enhance glucocorticoid receptor function in vitro by modulating the membrane steroid transporters.	2001 Nov	11704655
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
Clinical predictors of drug response in obsessive-compulsive disorder.	2001 Oct	11593074
Clomipramine discontinuation-emergent dystonia.	2001 Oct	11551294
Obsessive-compulsive symptoms during treatment with clozapine in a patient with schizophrenia.	2001 Oct	11551293
Ping-pong gaze in combined intoxication with tranylcypromine, thioridazine, and clomipramine.	2001 Oct-Dec	11725219
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
[Chronic discomfort with dentures - successful treatment with clomipramine].	2001 Sep	11678084
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
Antagonism of nicotinic acetylcholine receptors by inhibitors of monoamine uptake.	2001 Sep	11526465
Repeated but not acute clomipramine decreases the effect of N-methyl-D-aspartate receptor activation on serotonergic transmission between the raphe nuclei and frontal cortex.	2001 Sep	11522320
HPLC of basic drugs on microparticulate strong cation-exchange materials - a review.	2001 Sep 15	11516893
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
Effects of clomipramine on Trypanosoma cruzi infection in mice.	2001 Sep-Oct	11706667
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)`
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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