Clomipramine (CHEM002386)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (16)XML
Record Information
Version1.0
Creation Date2009-07-21 20:28:44 UTC
Update Date2026-05-14 16:59:03 UTC
Accession NumberCHEM002386
Identification
Common NameClomipramine
ClassSmall Molecule
DescriptionClomipramine, the 3-chloro analog of imipramine, is a dibenzazepine-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, clomipramine does not affect mood or arousal, but may cause sedation. In depressed individuals, clomipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as clomipramine, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline and desipramine. TCAs also down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine-H1 receptors, α1-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Clomipramine may be used to treat obsessive-compulsive disorder and disorders with an obsessive-compulsive component (e.g. depression, schizophrenia, Tourette's disorder). Unlabeled indications include panic disorder, chronic pain (e.g. central pain, idiopathic pain disorder, tension headache, diabetic peripheral neuropathy, neuropathic pain), cataplexy and associated narcolepsy, autistic disorder, trichotillomania, onchophagia, stuttering, premature ejaculation, and premenstrual syndrome. Clomipramine is rapidly absorbed from the gastrointestinal tract and demethylated in the liver to its primary active metabolite, desmethylclomipramine.
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
  • Suspected Compounds
  • T3DB toxins
  • ToxCast & Tox21 Chemicals
Contaminant Type
  • Amine
  • Antidepressive Agent, Tricyclic
  • Drug
  • Human Neurotoxin
  • Metabolite
  • Organic Compound
  • Organochloride
  • Serotonin Uptake Inhibitor
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
ValueSource
3-(3-Chloro-10,11-dihydro-5H-dibenzo[b,F]azepin-5-yl)-N,N-dimethyl-1-propanamineChEBI
3-(3-CHLORO-5H-dibenzo[b,F]azepin-5-yl)-N,N-dimethylpropan-1-amineChEBI
3-ChloroimipramineChEBI
ChlorimipramineChEBI
g 34586ChEBI
MonochlorimipramineChEBI
AnafranilKegg
Monohydrochloride, clomipramineHMDB
Clomipramine maleate (1:1)HMDB
Clomipramine monohydrochlorideHMDB
HydiphenHMDB
Hydrochloride, clomipramineHMDB
ChlomipramineHMDB
Clomipramine hydrochlorideHMDB
Chemical FormulaC19H23ClN2
Average Molecular Mass314.852 g/mol
Monoisotopic Mass314.155 g/mol
CAS Registry Number303-49-1
IUPAC Name(3-{14-chloro-2-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,12,14-hexaen-2-yl}propyl)dimethylamine
Traditional Nameclomipramine
SMILESCN(C)CCCN1C2=CC=CC=C2CCC2=C1C=C(Cl)C=C2
InChI IdentifierInChI=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
InChI KeyGDLIGKIOYRNHDA-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as dibenzazepines. Dibenzazepines are compounds with two benzene rings connected by an azepine ring. Azepine is an unsaturated seven-member heterocycle with one nitrogen atom replacing a carbon atom.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzazepines
Sub ClassDibenzazepines
Direct ParentDibenzazepines
Alternative Parents
Substituents
  • Dibenzazepine
  • Alkyldiarylamine
  • Tertiary aliphatic/aromatic amine
  • Azepine
  • Benzenoid
  • Aryl halide
  • Aryl chloride
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Organopnictogen compound
  • Amine
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point191.5-192°C
Boiling Point160-170°C at 3.00E-01 mm Hg
Solubility0.294 mg/L
Predicted Properties
PropertyValueSource
Water Solubility0.014 g/LALOGPS
logP5.04ALOGPS
logP4.88ChemAxon
logS-4.3ALOGPS
pKa (Strongest Basic)9.2ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area6.48 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity95.41 m³·mol⁻¹ChemAxon
Polarizability35.73 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-9060000000-34352b7b1b6a78a55cd8Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-052r-9010000000-77a0afe2d49df71431d8Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-014i-2009000000-a1cc70dad4bb4c19ab7bSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000i-9000000000-a9af3369f8d6da434fd0Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-052r-9000000000-3f1941447bc096ea9d73Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0a4r-9010000000-c6b5c5a56ac456cd8845Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0a4i-9010000000-8b5307526ea875a06881Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0a4i-9010000000-98746d4db184914ce871Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0a4i-9310000000-194486cca11709cd1b80Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0a4i-9600000000-da861dd5252aaff30e89Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0a4i-6900000000-efdead8e50e8b700d4bdSpectrum
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-00di-0090000000-558a68c9d4919e7945a2Spectrum
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-00di-0090000000-489c71d87d96f5bafd40Spectrum
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-014i-0009002000-3318f523b446a8d9d68eSpectrum
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-014i-0009000000-8b8a1763c5358415b2b0Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-0a4r-9000000000-5c2c7aa10719beb2c160Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-052r-9000000000-252b037815db33ff1554Spectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Positivesplash10-014i-4009000000-f6fbb8f3c1432560c648Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-000i-9000000000-96e4294b38c6773a9dffSpectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-014r-8009000000-47296607dea9797c1439Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-1029000000-68c9c186daeb14b564b2Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01bl-7095000000-7aeedc02e87a2acd87abSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0076-9140000000-201084960b40747f3339Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0009000000-0d5e3470f9eae466d2e1Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03fr-1089000000-bda0b94a0a3d33589f39Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0fbc-2390000000-f1f3b5dec72ac0b8b633Spectrum
MSMass Spectrum (Electron Ionization)splash10-066r-6391000000-e57dc447a97807ce527aSpectrum
Toxicity Profile
Route of ExposureWell absorbed from the GI tract following oral administration. Bioavailability is approximately 50% orally due to extensive first-pass metabolism. Bioavailability is not affected by food. Peak plasma concentrations occurred 2-6 hours following oral administration of a single 50 mg dose. The peak plasma concentration ranged from 56 ng/mL to 154 mg/mL (mean, 92 ng/mL). There are large interindividual variations in plasma concentrations occur, partly due to genetic differences in clomipramine metabolism. On average, steady state plasma concentrations are achieved in 1-2 weeks following multiple dose oral administration. Smoking appears to lower the steady-state plasma concentration of clomipramine, but not its active metabolite desmethylclomipramine.
Mechanism of ToxicityClomipramine is a strong, but not completely selective serotonin reuptake inhibitor (SRI), as the active main metabolite desmethyclomipramine acts preferably as an inhibitor of noradrenaline reuptake. α1-receptor blockage and β-down-regulation have been noted and most likely play a role in the short term effects of clomipramine. A blockade of sodium-channels and NDMA-receptors might, as with other tricyclics, account for its effect in chronic pain, in particular the neuropathic type.
MetabolismExtensively metabolized in the liver. The main active metabolite is desmethylclomipramine, which is formed by N-demethylation of clomipramine via CYP2C19, 3A4 and 1A2. Other metabolites and their glucuronide conjugates are also produced. Other metabolites of clomipramine include 8-hydroxyclomipramine formed via 8-hydroxylation, 2-hydroxyclomipramine formed via 2-hydroxylation, and clomipramine N-oxide formed by N-oxidation. Desmethylclomipramine is further metabolized to 8-hydroxydesmethylclomipramine and didesmethylclomipramine, which are formed by 8-hydroxylation and N-demethylation, respectively. 8-Hydroxyclomipramine and 8-hydroxydesmethylclomipramine are pharmacologically active; however, their clinical contribution remains unknown. Route of Elimination: Urine (51-60%) and feces via biliary elimination (24-32%) Half Life: Following oral administration of a single 150 mg dose of clomipramine, the average elimination half-life of clomipramine was 32 hours (range: 19-37 hours) and of desmethylclomipramine was 69 hours (range: 54-77 hours). Elimination half-life may vary substantially with different doses due to saturable kinetics (i.e. metabolism).
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesMay be used to treat obsessive-compulsive disorder and disorders with an obsessive-compulsive component (e.g. depression, schizophrenia, Tourette's disorder). Unlabeled indications include: depression, panic disorder, chronic pain (e.g. central pain, idiopathic pain disorder, tension headache, diabetic peripheral neuropathy, neuropathic pain), cataplexy and associated narcolepsy (limited evidence), autistic disorder (limited evidence), trichotillomania (limited evidence), onchophagia (limited evidence), stuttering (limited evidence), premature ejaculation, and premenstrual syndrome.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSigns and symptoms vary in severity depending upon factors such as the amount of drug absorbed, the age of the patient, and the time elapsed since drug ingestion. Critical manifestations of overdose include cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic toxicity. In U.S. clinical trials, 2 deaths occurred in 12 reported cases of acute overdosage with Anafranil either alone or in combination with other drugs. One death involved a patient suspected of ingesting a dose of 7000 mg. The second death involved a patient suspected of ingesting a dose of 5750 mg.
TreatmentObtain an ECG and immediately initiate cardiac monitoring. Protect the patient's airway, establish an intravenous line, and initiate gastric decontamination. A minimum of 6 hours of observation with cardiac monitoring and observation for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is necessary. If signs of toxicity occur at any time during this period, extended monitoring is required. (2)
Concentrations
Not Available
DrugBank IDDB01242
HMDB IDHMDB0015372
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDCXX
Wikipedia LinkClomipramine
Chemspider ID2699
ChEBI ID47780
PubChem Compound ID2801
Kegg Compound IDC06918
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

Schindler, W. and Dietrich, H.; US. Patent 3,515,785; June 2,1970; assigned to Geigy Chemical Corp.

MSDSLink
General References
1. FDA label
2. https://www.ncbi.nlm.nih.gov/pubmed/?term=12007764
3. https://www.ncbi.nlm.nih.gov/pubmed/?term=12084414
4. https://www.ncbi.nlm.nih.gov/pubmed/?term=16085036
5. https://www.ncbi.nlm.nih.gov/pubmed/?term=17471183
6. https://www.ncbi.nlm.nih.gov/pubmed/?term=19747949
7. https://www.ncbi.nlm.nih.gov/pubmed/?term=19810911