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Identification
NameClomipramine
Accession NumberDB01242  (APRD00253, DB07600)
Typesmall molecule
Groupsapproved
Description

Clomipramine, 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.

Structure
Thumb
Synonyms
SynonymLanguageCode
3-ChloroimipramineNot AvailableNot Available
ChlorimipramineNot AvailableNot Available
ClomipraminaSpanishINN
ClomipraminumLatinINN
MonochlorimipramineNot AvailableNot Available
Salts
Name/CAS Structure Properties
Clomipramine Hydrochloride
17321-77-6
Thumb
  • InChI Key: WIMWMKZEIBHDTH-UHFFFAOYSA-N
  • Monoisotopic Mass: 350.131654192
  • Average Mass: 351.313
DBSALT000028
Brand names
NameCompany
AnafranilNovartis
HydiphenArzneimittelwerk Dresden
Brand mixturesNot Available
Categories
CAS number303-49-1
WeightAverage: 314.852
Monoisotopic: 314.154976453
Chemical FormulaC19H23ClN2
InChI KeyInChIKey=GDLIGKIOYRNHDA-UHFFFAOYSA-N
InChI
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
IUPAC Name
(3-{5-chloro-2-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl}propyl)dimethylamine
SMILES
CN(C)CCCN1C2=CC=CC=C2CCC2=C1C=C(Cl)C=C2
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzazepines
SubclassDibenzazepines
Direct parentDibenzazepines
Alternative parentsChlorobenzenes; Azepines; Aryl Chlorides; Tertiary Amines; Polyamines; Organochlorides
Substituentschlorobenzene; azepine; benzene; aryl halide; aryl chloride; tertiary amine; polyamine; organochloride; organohalogen; amine; organonitrogen compound
Classification descriptionThis compound belongs to the dibenzazepines. These are compounds with two benzene rings connected by an azepine ring.
Pharmacology
IndicationMay 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.
PharmacodynamicsClomipramine, a tricyclic antidepressant, is the 3-chloro derivative of Imipramine. It was thought that tricyclic antidepressants work exclusively by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: α1 and β1 receptors are sensitized, α2 receptors are desensitized (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain.
Mechanism of actionClomipramine 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.
AbsorptionWell 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.
Volume of distribution

~ 17 L/kg (range: 9-25 L/kg).
Clomipramine is capable of distributing into the cerebrospinal fluid, the brain, and into breast milk.

Protein bindingClomipramine is approximately 97-98% bound to plasma proteins, principally to albumin and possibly to α1-acid glycoprotein. Desmethylclomipramine is 97-99% bound to plasma proteins.
Metabolism

Extensively metabolized in the liver. The main active metabolite is desmethylclomipramine, which is formed by <i>N</i>-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 <i>N</i>-oxide formed by <i>N</i>-oxidation. Desmethylclomipramine is further metabolized to 8-hydroxydesmethylclomipramine and didesmethylclomipramine, which are formed by 8-hydroxylation and <i>N</i>-demethylation, respectively. 8-Hydroxyclomipramine and 8-hydroxydesmethylclomipramine are pharmacologically active; however, their clinical contribution remains unknown.

SubstrateEnzymesProduct
Clomipramine
desmethylclomipramineDetails
Clomipramine
2-hydroxyclomipramineDetails
Clomipramine
8-hydroxyclomipramineDetails
Clomipramine
    clomipramine N-oxideDetails
    desmethylclomipramine
    didesmethylclomipramineDetails
    2-hydroxyclomipramine
    2-hydroxydesmethyl clomipramineDetails
    2-hydroxyclomipramine
      2-hydroxyclomipramine glucuronideDetails
      8-hydroxyclomipramine
        8-hydroxyclomipramine glucuronideDetails
        8-hydroxyclomipramine
          8-hydroxydesmethyl clomipramineDetails
          2-hydroxydesmethyl clomipramine
            2-hydroxydesmethyl clomipramine glucuronideDetails
            8-hydroxydesmethyl clomipramine
              8-hyroxydesmethyl clomipramine glucuronideDetails
              Route of eliminationUrine (51-60%) and feces via biliary elimination (24-32%)
              Half lifeFollowing 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).
              ClearanceNot Available
              ToxicitySigns 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. Side effects include: sedation, hypotension, blurred vision, dry mouth, constipation, urinary retention, postural hypotension, tachycardia, hypertension, ECG changes, heart failure, impaired memory and delirium, and precipitation of hypomanic or manic episodes in bipolar depression. Withdrawal symptoms include gastrointestinal disturbances, anxiety, and insomnia.
              Affected organisms
              • Humans and other mammals
              Pathways
              PathwayCategorySMPDB ID
              Clomipramine Metabolism PathwayDrug metabolismSMP00639
              SNP Mediated Effects
              Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
              Cytochrome P450 2D6
              Gene symbol: CYP2D6
              UniProt: P10635
              rs3892097 CYP2D6*4A AllelePoor drug metabolizer, lower dose requirements, higher risk for adverse side effects18070221
              SNP Mediated Adverse Drug Reactions
              Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeAdverse ReactionReference(s)
              Cytochrome P450 2D6
              Gene symbol: CYP2D6
              UniProt: P10635
              rs3892097 CYP2D6*4C > TThose that are homozygous for the poorly metabolizing CYP2D6 alleles are at an increased risk of side effects and decrease drug metabolism18070221
              Cytochrome P450 2D6
              Gene symbol: CYP2D6
              UniProt: P10635
              rs3892097 CYP2D6*4C > TThose that are homozygous for the poorly metabolizing CYP2D6 alleles are at an increased risk of side effects and decrease drug metabolism9918137
              ADMET
              Predicted ADMET features
              Property Value Probability
              Human Intestinal Absorption + 0.9843
              Blood Brain Barrier + 0.9793
              Caco-2 permeable + 0.8391
              P-glycoprotein substrate Substrate 0.7618
              P-glycoprotein inhibitor I Inhibitor 0.8573
              P-glycoprotein inhibitor II Inhibitor 0.8387
              Renal organic cation transporter Inhibitor 0.852
              CYP450 2C9 substrate Non-substrate 0.7875
              CYP450 2D6 substrate Substrate 0.8918
              CYP450 3A4 substrate Substrate 0.7408
              CYP450 1A2 substrate Inhibitor 0.8374
              CYP450 2C9 substrate Non-inhibitor 0.9176
              CYP450 2D6 substrate Inhibitor 0.8932
              CYP450 2C19 substrate Non-inhibitor 0.9025
              CYP450 3A4 substrate Non-inhibitor 0.7971
              CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6074
              Ames test Non AMES toxic 0.8735
              Carcinogenicity Non-carcinogens 0.8971
              Biodegradation Not ready biodegradable 0.9967
              Rat acute toxicity 2.7426 LD50, mol/kg Not applicable
              hERG inhibition (predictor I) Weak inhibitor 0.889
              hERG inhibition (predictor II) Inhibitor 0.8029
              Pharmacoeconomics
              Manufacturers
              • Tyco healthcare group lp
              • Mylan pharmaceuticals inc
              • Sandoz inc
              • Taro pharmaceutical industries ltd
              • Teva pharmaceuticals usa inc
              • Watson laboratories inc
              Packagers
              Dosage forms
              FormRouteStrength
              CapsuleOral25 mg, 50 mg, 75 mg
              Prices
              Unit descriptionCostUnit
              Clomipramine hcl powder17.88USDg
              Anafranil 25 mg capsule13.51USDcapsule
              Anafranil 50 mg capsule13.51USDcapsule
              Anafranil 75 mg capsule13.24USDcapsule
              ClomiPRAMINE HCl 75 mg capsule1.55USDcapsule
              Clomipramine 75 mg capsule1.33USDcapsule
              Clomipramine 50 mg capsule1.01USDcapsule
              ClomiPRAMINE HCl 25 mg capsule0.88USDcapsule
              Anafranil 50 mg Tablet0.77USDtablet
              Clomipramine 25 mg capsule0.75USDcapsule
              ClomiPRAMINE HCl 50 mg capsule0.57USDcapsule
              Apo-Clomipramine 50 mg Tablet0.43USDtablet
              Co Clomipramine 50 mg Tablet0.43USDtablet
              Anafranil 25 mg Tablet0.42USDtablet
              Anafranil 10 mg Tablet0.31USDtablet
              Apo-Clomipramine 25 mg Tablet0.23USDtablet
              Co Clomipramine 25 mg Tablet0.23USDtablet
              Apo-Clomipramine 10 mg Tablet0.17USDtablet
              Co Clomipramine 10 mg Tablet0.17USDtablet
              DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
              PatentsNot Available
              Properties
              Statesolid
              Experimental Properties
              PropertyValueSource
              melting point191.5-192Schindler, W. and Dietrich, H.; US. Patent 3,515,785; June 2,1970; assigned to Geigy Chemical Corp.
              boiling point160-170 °C at 3.00E-01 mm HgPhysProp
              water solubility0.294 mg/LNot Available
              logP5.19HANSCH,C ET AL. (1995)
              Predicted Properties
              PropertyValueSource
              water solubility1.44e-02 g/lALOGPS
              logP5.04ALOGPS
              logP4.88ChemAxon
              logS-4.3ALOGPS
              pKa (strongest basic)9.2ChemAxon
              physiological charge1ChemAxon
              hydrogen acceptor count2ChemAxon
              hydrogen donor count0ChemAxon
              polar surface area6.48ChemAxon
              rotatable bond count4ChemAxon
              refractivity95.41ChemAxon
              polarizability35.73ChemAxon
              number of rings3ChemAxon
              bioavailability1ChemAxon
              rule of fiveYesChemAxon
              Ghose filterYesChemAxon
              Veber's ruleYesChemAxon
              MDDR-like ruleNoChemAxon
              Spectra
              SpectraNot Available
              References
              Synthesis Reference

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

              General Reference
              1. FDA label
              External Links
              ResourceLink
              KEGG DrugD00811
              KEGG CompoundC06918
              BindingDB50021927
              ChEBI47780
              ChEMBLCHEMBL415
              Therapeutic Targets DatabaseDAP000742
              PharmGKBPA449048
              IUPHAR2398
              Guide to Pharmacology2398
              HETCXX
              Drug Product Database2244818
              RxListhttp://www.rxlist.com/cgi/generic/clomipr.htm
              Drugs.comhttp://www.drugs.com/cdi/clomipramine.html
              PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/ana1020.shtml
              WikipediaClomipramine
              ATC CodesN06AA04
              AHFS Codes
              • 28:16.04.28
              PDB EntriesNot Available
              FDA labelshow(712 KB)
              MSDSshow(74.2 KB)
              Interactions
              Drug Interactions
              Drug
              AltretamineRisk of severe hypotension
              ArtemetherAdditive QTc-prolongation may occur. Concomitant therapy should be avoided.
              AtazanavirAtazanavir may increase the effect and toxicity of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if atazanavir is initiated, discontinued or dose changed.
              ButabarbitalBarbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like clomipramine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
              ButalbitalBarbiturates such as butalbital may increase the metabolism of tricyclic antidepressants such as clomipramine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
              CimetidineCimetidine may increase the effect of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if cimetidine is initiated, discontinued or dose changed.
              CisaprideIncreased risk of cardiotoxicity and arrhythmias
              ClonidineThe tricyclic antidepressant, clomipramine, may decrease the effect of clonidine.
              DesvenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
              Dihydroquinidine barbiturateDihydroquinidine barbiturate increases the effect of the tricyclic antidepressant, clomipramine.
              DobutamineThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of dobutamine.
              DonepezilPossible antagonism of action
              DopamineThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of dopamine.
              EphedraThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of ephedra.
              EphedrineThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of ephedrine.
              EpinephrineThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of epinephrine.
              FenoterolThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of fenoterol.
              FluoxetineThe SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of clomipramine if fluoxetine is initiated, discontinued or dose changed.
              FluvoxamineThe SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of clomipramine if fluvoxamine is initiated, discontinued or dose changed.
              GalantaminePossible antagonism of action
              GrepafloxacinIncreased risk of cardiotoxicity and arrhythmias
              GuanethidineThe tricyclic antidepressant, clomipramine, decreases the effect of guanethidine.
              IsocarboxazidPossibility of severe adverse effects
              IsoprenalineThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of isoproterenol.
              MephentermineThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of mephentermine.
              MetaraminolThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of metaraminol.
              MethoxamineThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of methoxamine.
              MoclobemidePossible severe adverse reaction with this combination
              NorepinephrineThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of norepinephrine.
              OrciprenalineThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of orciprenaline.
              PhenelzinePossibility of severe adverse effects
              PhenylephrineThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of phenylephrine.
              PhenylpropanolamineThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of phenylpropanolamine.
              PirbuterolThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of pirbuterol.
              ProcaterolThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of procaterol.
              PseudoephedrineThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of pseudoephedrine.
              QuinidineAdditive QTc-prolonging effects may occur. Quinidine may also increase the serum concentration of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if quinidine is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy.
              Quinidine barbiturateQuinidine barbiturate increases the effect of tricyclic antidepressant, clomipramine.
              RasagilinePossibility of severe adverse effects
              RifabutinThe rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, clomipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if rifabutin is initiated, discontinued or dose changed.
              RifampicinThe rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, clomipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if rifampin is initiated, discontinued or dose changed.
              RitonavirRitonavir may increase the effect and toxicity of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if ritonavir if initiated, discontinued or dose changed.
              RivastigminePossible antagonism of action
              SalbutamolThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of salbutamol.
              SibutramineIncreased risk of CNS adverse effects
              SparfloxacinIncreased risk of cardiotoxicity and arrhythmias
              TacrineThe therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Clomipramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
              TacrolimusAdditive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
              TamoxifenClomipramine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
              TamsulosinClomipramine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Clomipramine is initiated, discontinued, or dose changed.
              TerbinafineTerbinafine may reduce the metabolism and clearance of Clomipramine. Consider alternate therapy or monitor for therapeutic/adverse effects of Clomipramine if Terbinafine is initiated, discontinued or dose changed.
              TerbutalineThe tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of terbutaline.
              TerfenadineIncreased risk of cardiotoxicity and arrhythmias
              ThiabendazoleThe strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Clomipramine by decreasing Clomipramine metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Clomipramine if Thiabendazole is initiated, discontinued or dose changed.
              ThiothixeneMay cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
              TiclopidineTiclopidine may decrease the metabolism and clearance of Clomipramine. Consider alternate therapy or monitor for adverse/toxic effects of Clomipramine if Ticlopidine is initiated, discontinued or dose changed.
              ToremifeneAdditive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
              TramadolTramadol increases the risk of serotonin syndrome and seizures. Clomipramine may decrease the effect of Tramadol by decreasing active metabolite production.
              TranylcypromineIncreased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.
              TrazodoneIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
              TrimethobenzamideTrimethobenzamide and Clomipramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
              TrimipramineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
              TriprolidineTriprolidine and Clomipramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
              TrospiumTrospium and Clomipramine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
              VenlafaxineIncreased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
              VoriconazoleAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
              VorinostatAdditive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
              ZiprasidoneAdditive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
              ZolmitriptanUse of two serotonin modulators, such as zolmitriptan and clomipramine, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
              ZuclopenthixolAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
              Zuclopenthixol acetateAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
              Zuclopenthixol decanoateAdditive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
              Food Interactions
              • Avoid alcohol.
              • Grapefruit and grapefruit juice should be avoided throughout treatment, grapefruit can modify serum levels of clomipramine and its metabolite desmethyl-clomipramine.
              • Take with food to reduce irritation.

              1. Sodium-dependent serotonin transporter

              Kind: protein

              Organism: Human

              Pharmacological action: yes

              Actions: inhibitor

              Components

              Name UniProt ID Details
              Sodium-dependent serotonin transporter P31645 Details

              References:

              1. Alvarez JC, Gluck N, Arnulf I, Quintin P, Leboyer M, Pecquery R, Launay JM, Perez-Diaz F, Spreux-Varoquaux O: Decreased platelet serotonin transporter sites and increased platelet inositol triphosphate levels in patients with unipolar depression: effects of clomipramine and fluoxetine. Clin Pharmacol Ther. 1999 Dec;66(6):617-24. Pubmed
              2. Borkowska A, Pilaczynska E, Araszkiewicz A, Rybakowski J: [The effect of sertraline on cognitive functions in patients with obsessive-compulsive disorder] Psychiatr Pol. 2002 Nov-Dec;36(6 Suppl):289-95. Pubmed
              3. Suhara T, Takano A, Sudo Y, Ichimiya T, Inoue M, Yasuno F, Ikoma Y, Okubo Y: High levels of serotonin transporter occupancy with low-dose clomipramine in comparative occupancy study with fluvoxamine using positron emission tomography. Arch Gen Psychiatry. 2003 Apr;60(4):386-91. Pubmed
              4. Larsen AK, Brennum LT, Egebjerg J, Sanchez C, Halldin C, Andersen PH: Selectivity of (3)H-MADAM binding to 5-hydroxytryptamine transporters in vitro and in vivo in mice; correlation with behavioural effects. Br J Pharmacol. 2004 Mar;141(6):1015-23. Epub 2004 Mar 1. Pubmed
              5. Malizia AL, Melichar JM, Brown DJ, Gunn RN, Reynolds A, Jones T, Nutt DJ: Demonstration of clomipramine and venlafaxine occupation at serotonin reuptake sites in man in vivo. J Psychopharmacol. 1997;11(3):279-81. Pubmed
              6. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. Pubmed
              7. Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. Pubmed

              2. 5-hydroxytryptamine receptor 2A

              Kind: protein

              Organism: Human

              Pharmacological action: yes

              Actions: antagonist

              Components

              Name UniProt ID Details
              5-hydroxytryptamine receptor 2A P28223 Details

              References:

              1. Hentall ID, Kurle PJ, White TR: Correlations between serotonin level and single-cell firing in the rat’s nucleus raphe magnus. Neuroscience. 2000;95(4):1081-8. Pubmed
              2. Contreras CM, Marvan ML, Munoz-Mendez A, Ramirez-Morales A: Cortical and septal responses to dorsal raphe nucleus stimulation in the rat: long-term clomipramine actions. Bol Estud Med Biol. 1992 Jan-Dec;40(1-4):3-7. Pubmed
              3. Sugimoto Y, Inoue K, Yamada J: The tricyclic antidepressant clomipramine increases plasma glucose levels of mice. J Pharmacol Sci. 2003 Sep;93(1):74-9. Pubmed
              4. Trifunovic RD, Brodie MS: The effects of clomipramine on the excitatory action of ethanol on dopaminergic neurons of the ventral tegmental area in vitro. J Pharmacol Exp Ther. 1996 Jan;276(1):34-40. Pubmed
              5. Sargent PA, Quested DJ, Cowen PJ: Clomipramine enhances the cortisol response to 5-HTP: implications for the therapeutic role of 5-HT2 receptors. Psychopharmacology (Berl). 1998 Nov;140(1):120-2. Pubmed

              3. 5-hydroxytryptamine receptor 2B

              Kind: protein

              Organism: Human

              Pharmacological action: yes

              Actions: antagonist

              Components

              Name UniProt ID Details
              5-hydroxytryptamine receptor 2B P41595 Details

              References:

              1. Sargent PA, Quested DJ, Cowen PJ: Clomipramine enhances the cortisol response to 5-HTP: implications for the therapeutic role of 5-HT2 receptors. Psychopharmacology (Berl). 1998 Nov;140(1):120-2. Pubmed
              2. Sugimoto Y, Inoue K, Yamada J: The tricyclic antidepressant clomipramine increases plasma glucose levels of mice. J Pharmacol Sci. 2003 Sep;93(1):74-9. Pubmed
              3. Contreras CM, Marvan ML, Munoz-Mendez A, Ramirez-Morales A: Cortical and septal responses to dorsal raphe nucleus stimulation in the rat: long-term clomipramine actions. Bol Estud Med Biol. 1992 Jan-Dec;40(1-4):3-7. Pubmed

              4. 5-hydroxytryptamine receptor 2C

              Kind: protein

              Organism: Human

              Pharmacological action: yes

              Actions: antagonist

              Components

              Name UniProt ID Details
              5-hydroxytryptamine receptor 2C P28335 Details

              References:

              1. Sargent PA, Quested DJ, Cowen PJ: Clomipramine enhances the cortisol response to 5-HTP: implications for the therapeutic role of 5-HT2 receptors. Psychopharmacology (Berl). 1998 Nov;140(1):120-2. Pubmed
              2. Sugimoto Y, Inoue K, Yamada J: The tricyclic antidepressant clomipramine increases plasma glucose levels of mice. J Pharmacol Sci. 2003 Sep;93(1):74-9. Pubmed
              3. Contreras CM, Marvan ML, Munoz-Mendez A, Ramirez-Morales A: Cortical and septal responses to dorsal raphe nucleus stimulation in the rat: long-term clomipramine actions. Bol Estud Med Biol. 1992 Jan-Dec;40(1-4):3-7. Pubmed

              5. Sodium-dependent noradrenaline transporter

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: inhibitor

              Components

              Name UniProt ID Details
              Sodium-dependent noradrenaline transporter P23975 Details

              References:

              1. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. Pubmed
              2. Jungkun G, Kuss HJ, Gsell W: Long-term effects of tricyclic antidepressants on norepinephrine kinetics in humans. J Neural Transm. 2001;108(3):349-62. Pubmed

              6. Glutathione S-transferase P

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: inhibitor

              Components

              Name UniProt ID Details
              Glutathione S-transferase P P09211 Details

              References:

              1. Baranczyk-Kuzma A, Sawicki J, Kuzma M, Jagiello J: [Tricyclic antidepressants as inhibitors of brain glutathione-S-transferase] Pol Merkur Lekarski. 2001 Dec;11(66):472-5. Pubmed
              2. Baranczyk-Kuzma A, Kuzma M, Gutowicz M, Kazmierczak B, Sawicki J: Glutathione S-transferase pi as a target for tricyclic antidepressants in human brain. Acta Biochim Pol. 2004;51(1):207-12. Pubmed
              3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

              7. Transporter

              Kind: protein

              Organism: Aquifex aeolicus (strain VF5)

              Pharmacological action: unknown

              Components

              Name UniProt ID Details
              Transporter O67854 Details

              References:

              1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

              1. Cytochrome P450 2D6

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: substrate inhibitor

              Components

              Name UniProt ID Details
              Cytochrome P450 2D6 P10635 Details

              References:

              1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
              2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

              2. Cytochrome P450 2C19

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: substrate

              Components

              Name UniProt ID Details
              Cytochrome P450 2C19 P33261 Details

              References:

              1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
              2. Application available online: The P450 Program
              3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

              3. Cytochrome P450 1A2

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: substrate

              Components

              Name UniProt ID Details
              Cytochrome P450 1A2 P05177 Details

              References:

              1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
              2. http://www.mentalhealth.com/drug/p30-a01.html Source
              3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

              4. Cytochrome P450 3A4

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: substrate

              Components

              Name UniProt ID Details
              Cytochrome P450 3A4 P08684 Details

              References:

              1. Application available online: The P450 Program
              2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

              1. Serum albumin

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: substrate

              Components

              Name UniProt ID Details
              Serum albumin P02768 Details

              References:

              1. FDA label

              1. Multidrug resistance protein 1

              Kind: protein

              Organism: Human

              Pharmacological action: unknown

              Actions: inhibitor

              Components

              Name UniProt ID Details
              Multidrug resistance protein 1 P08183 Details

              References:

              1. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. Pubmed

              Comments
              Drug created on June 13, 2005 07:24 / Updated on April 08, 2014 11:10