CLOMIPRAMINE HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H23ClN2.ClH
Molecular Weight	351.313
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=WIMWMKZEIBHDTH-UHFFFAOYSA-N

InChI=1S/C19H23ClN2.ClH/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;1H

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

Molecular Formula	ClH
Molecular Weight	36.461
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 8297

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 8429	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 1989

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 1737	substrate 1037	substrate 1217	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 OCT1 512	CYP1A1 349 CYP1A2 1054 CYP2C8 693 CYP2C18 138 CYP2C19 991 UGT2B10 127 UGT1A4 347

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
OCT1 543	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/18788725/	yes
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/21718296/	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
UGT2B10 127	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20133892/	major
UGT1A4 347	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20133892/	minor
CYP1A1 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/	no
CYP2C18 138	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/	no
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/	no
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/	no
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/	yes
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8667235/	yes
CYP2C19 991	substrate 3367 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 1217	substrate 3367 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 1647	inhibitor 1626 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
Letter: Clonazepam in the treatment of drug-induced dyskinesia.	1975 Feb 1	1111773
Delirious episodes induced by intravenous administration of clomipramine associated with an acute increase in its plasma concentrations.	2000 Dec	11145466
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
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
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
[A case of 'hallucination of soliloquy' with hypothyroidism induced Hashimoto disease. Meaning of psychopathological research about symptomatic psychosis].	2001	11326441
Development of a depersonalization severity scale.	2001 Apr	11469161
Use of clomipramine in treatment of obsessive-compulsive disorder, separation anxiety and noise phobia in dogs: a preliminary, clinical study.	2001 Apr	11349411
Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients.	2001 Aug	11477329
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
Selected tricyclic antidepressant ingestions involving children 6 years old or less.	2001 Feb	11157289
Auditory P300 event related potential and serotonin reuptake inhibitor treatment in obsessive-compulsive disorder patients.	2001 Feb 14	11223122
Lithium therapy for corticosteroid-induced mood disorder.	2001 Jan	11235931
Therapeutic effects and long-term efficacy of antidepressant medication for persons with developmental disabilities. Behavioral assessment in two cases of treatment-resistant aggression and self-injury.	2001 Jan	11151486
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
Clomipramine--beyond separation anxiety.	2001 Jul-Aug	11450830
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
Placebo affects the performance of rats in models of depression: is it a good control for behavioral experiments?	2001 Jun	11418280
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
The serotonergic 5-HT(2C) agonist m-chlorophenylpiperazine increases weight-supported locomotion without development of tolerance in rats with spinal transections.	2001 Jun	11358463
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
Antinociceptive effect of clomipramine in monoarthritic rats as revealed by the paw pressure test and the C-fiber-evoked reflex.	2001 Mar 23	11282112
Possible mild serotonin syndrome related to co-prescription of tandospirone and trazodone.	2001 Mar-Apr	11354048
Long-term effects of clomipramine and fluoxetine on dorsal periaqueductal grey-evoked innate defensive behaviours of the rat.	2001 May	11432688
Olanzapine augmentation of serotonin uptake inhibitors in obsessive-compulsive disorder: an open study.	2001 May	11387793
A meta-analysis of the efficacy and tolerability of paroxetine versus tricyclic antidepressants in the treatment of major depression.	2001 May	11354239
Assessment of the serotonin and norepinephrine reuptake blocking properties of duloxetine in healthy subjects.	2001 May	11282251
[A classic antidepressant as an analgesic. Chronic pain under secure control].	2001 May 28	11434267
[Narcolepsy in a prepubertal boy].	2001 Nov	11725521
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
[Chronic discomfort with dentures - successful treatment with clomipramine].	2001 Sep	11678084
Comment: serotonin syndrome and 5-HT2A antagonism.	2001 Sep	11573872
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 `Fri Dec 15 16:21:09 GMT 2023` Edited by `admin` on `Fri Dec 15 16:21:09 GMT 2023`
Record UNII	2LXW0L6GWJ
Record Status	`Validated (UNII)`
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Name

Type

Language

CLOMIPRAMINE HYDROCHLORIDE

Official Name

English

CLOMIPRAMINE HYDROCHLORIDE [USP-RS]

Common Name

English

Clomipramine hydrochloride [WHO-DD]

Common Name

English

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

Common Name

English

CLOMIPRAMINE HYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

CLOMIPRAMINE HYDROCHLORIDE [GREEN BOOK]

Common Name

English

CLOMIPRAMINE HYDROCHLORIDE [USAN]

Common Name

English

NSC-759323

Code

English

CLOMIPRAMINE HCL

Common Name

English

G-34586

Code

English

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

Systematic Name

English

CLOMIPRAMINE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

CLOMIPRAMINE HYDROCHLORIDE [MART.]

Common Name

English

CLOMIPRAMINE HYDROCHLORIDE [MI]

Common Name

English

CLOMIPRAMINE HYDROCHLORIDE [EP MONOGRAPH]

Common Name

English

CLOMIPRAMINE HYDROCHLORIDE [VANDF]

Common Name

English

CLOMIPRAMINE HYDROCHLORIDE [JAN]

Common Name

English

ANAFRANIL

Brand Name

English

G 34586

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C94727