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Identification
- Summary
Clomipramine is a tricyclic antidepressant used in the treatment of obsessive-compulsive disorder and disorders with an obsessive-compulsive component, such as depression, schizophrenia, and Tourette’s disorder.
- Brand Names
- Anafranil
- Generic Name
- Clomipramine
- DrugBank Accession Number
- DB01242
- Background
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.
- Type
- Small Molecule
- Groups
- Approved, Investigational, Vet approved
- Structure
Structure for Clomipramine (DB01242)
- Weight
- Average: 314.852
Monoisotopic: 314.154976453 - Chemical Formula
- C19H23ClN2
- Synonyms
- 3-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethyl-1-propanamine
- 3-(3-chloro-5H-dibenzo[b,F]azepin-5-yl)-N,N-dimethylpropan-1-amine
- 3-Chloroimipramine
- Chlorimipramine
- Clomipramina
- Clomipramine
- Clomipraminum
- Monochlorimipramine
- External IDs
- NSC-169865
Pharmacology
- Indication
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: 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.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Depression ••• ••••• Management of Obsessive-compulsive disorder •••••••••••• Treatment of Panic disorder ••• ••••• - Contraindications & Blackbox Warnings
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Clomipramine, 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 action
Clomipramine 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.
Target Actions Organism ASodium-dependent serotonin transporter inhibitorHumans A5-hydroxytryptamine receptor 2A antagonistHumans A5-hydroxytryptamine receptor 2B antagonistHumans A5-hydroxytryptamine receptor 2C antagonistHumans USodium-dependent noradrenaline transporter inhibitorHumans UGlutathione S-transferase P inhibitorHumans - Absorption
Well 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 binding
Clomipramine 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 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 relevance remains unknown.
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- 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).
- Clearance
Not Available
- Adverse Effects
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Signs 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.
- Pathways
Pathway Category Clomipramine Metabolism Pathway Drug metabolism - Pharmacogenomic Effects/ADRs
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Cytochrome P450 2D6 CYP2D6*4 (A;A) A Allele Effect Directly Studied Patients with this genotype have reduced metabolism of clomipramine. Details Cytochrome P450 2D6 CYP2D6*3 Not Available 2549delA Effect Directly Studied The presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of clomipramine. Details Cytochrome P450 2D6 CYP2D6*4 Not Available A allele Effect Directly Studied The presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of clomipramine. Details Cytochrome P450 2D6 CYP2D6*5 Not Available Whole-gene deletion Effect Directly Studied The presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of clomipramine. Details Cytochrome P450 2D6 CYP2D6*6 Not Available 1707delT Effect Directly Studied The presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of clomipramine. Details Cytochrome P450 2C19 CYP2C19*2 Not Available 681G>A Effect Directly Studied The presence of this polymorphism in CYP2C19 is associated with poor metabolism of clomipramine. Details Cytochrome P450 2C19 CYP2C19*3 Not Available 636G>A Effect Directly Studied The presence of this polymorphism in CYP2C19 is associated with reduced or poor metabolism of clomipramine. Details Cytochrome P450 2D6 CYP2D6*7 Not Available 2935A>C Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*8 Not Available 1758G>T Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*11 Not Available 883G>C Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*12 Not Available 124G>A Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*13 Not Available CYP2D7/2D6 hybrid gene structure Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*14A Not Available 1758G>A Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*15 Not Available 137insT, 137_138insT Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*19 Not Available 2539_2542delAACT Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*20 Not Available 1973_1974insG Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*21 Not Available 2573insC Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*31 Not Available -1770G>A / -1584C>G … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*36 Not Available 100C>T / -1426C>T … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*38 Not Available 2587_2590delGACT Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*40 Not Available 1863_1864ins(TTT CGC CCC)2 Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*42 Not Available 3259_3260insGT Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*44 Not Available 2950G>C Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*47 Not Available 100C>T / -1426C>T … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*51 Not Available -1584C>G / -1235A>G … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*56 Not Available 3201C>T Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*57 Not Available 100C>T / 310G>T … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*62 Not Available 4044C>T Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*68A Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*68B Not Available Similar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4. Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*69 Not Available 2988G>A / -1426C>T … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*92 Not Available 1995delC Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*100 Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*101 Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended. Details Cytochrome P450 2C19 CYP2C19*2A Not Available 681G>A Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended. Details Cytochrome P450 2C19 CYP2C19*2B Not Available 681G>A Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended. Details Cytochrome P450 2C19 CYP2C19*4 Not Available 1A>G Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended. Details Cytochrome P450 2C19 CYP2C19*5 Not Available 1297C>T Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended. Details Cytochrome P450 2C19 CYP2C19*6 Not Available 395G>A Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended. Details Cytochrome P450 2C19 CYP2C19*7 Not Available 19294T>A Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended. Details Cytochrome P450 2C19 CYP2C19*22 Not Available 557G>C / 991A>G Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended. Details Cytochrome P450 2C19 CYP2C19*24 Not Available 99C>T / 991A>G … show all Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended. Details Cytochrome P450 2C19 CYP2C19*35 Not Available 12662A>G Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*3 Not Available C allele Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*5 Not Available Whole-gene deletion Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*6 Not Available 1707delT Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*7 Not Available 2935A>C Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*8 Not Available 1758G>T Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*11 Not Available 883G>C Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*12 Not Available 124G>A Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*13 Not Available CYP2D7/2D6 hybrid gene structure Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*14A Not Available 1758G>A Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*15 Not Available 137insT, 137_138insT Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*19 Not Available 2539_2542delAACT Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*20 Not Available 1973_1974insG Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*21 Not Available 2573insC Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*31 Not Available -1770G>A / -1584C>G … show all Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*36 Not Available 100C>T / -1426C>T … show all Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*38 Not Available 2587_2590delGACT Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*40 Not Available 1863_1864ins(TTT CGC CCC)2 Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*42 Not Available 3259_3260insGT Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*44 Not Available 2950G>C Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*47 Not Available 100C>T / -1426C>T … show all Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*51 Not Available -1584C>G / -1235A>G … show all Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*56 Not Available 3201C>T Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*57 Not Available 100C>T / 310G>T … show all Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*62 Not Available 4044C>T Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*68A Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*68B Not Available Similar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4. Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*69 Not Available 2988G>A / -1426C>T … show all Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*92 Not Available 1995delC Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*100 Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*101 Not Available -1426C>T / -1235A>G … show all Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for adverse side effects Details Cytochrome P450 2D6 CYP2D6*3 Not Available G allele Effect Directly Studied The presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of clomipramine. Details Cytochrome P450 2D6 CYP2D6*4 Not Available 3877G>A Effect Directly Studied The presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of clomipramine. Details
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Clomipramine is combined with 1,2-Benzodiazepine. Abacavir Abacavir may decrease the excretion rate of Clomipramine which could result in a higher serum level. Abaloparatide The risk or severity of adverse effects can be increased when Clomipramine is combined with Abaloparatide. Abametapir The serum concentration of Clomipramine can be increased when it is combined with Abametapir. Abatacept The metabolism of Clomipramine can be increased when combined with Abatacept. - Food Interactions
- Avoid alcohol.
- Avoid grapefruit products.
- Take with food. Food reduces irritation.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Clomipramine hydrochloride 2LXW0L6GWJ 17321-77-6 WIMWMKZEIBHDTH-UHFFFAOYSA-N - Product Images
- International/Other Brands
- Anapramine / Hydiphen (Arzneimittelwerk Dresden)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Act Clomipramine Tablet 50 mg Oral Actavis Pharma Company 2003-02-20 2016-02-19 Canada 
Act Clomipramine Tablet 25 mg Oral Actavis Pharma Company 2003-02-20 2016-02-19 Canada Act Clomipramine Tablet 10 mg Oral Actavis Pharma Company 2003-02-20 2016-02-19 Canada Anafranil Tablet 50 mg Oral Apotex Corporation 1981-12-31 Not applicable Canada Anafranil Capsule 75 mg/1 Oral Physicians Total Care, Inc. 1989-09-29 2002-06-30 US 
- Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Altius-clomipramine Tablet 10 mg Oral Aspri Pharma Canada Inc Not applicable Not applicable Canada Altius-clomipramine Tablet 50 mg Oral Aspri Pharma Canada Inc Not applicable Not applicable Canada Altius-clomipramine Tablet 25 mg Oral Aspri Pharma Canada Inc Not applicable Not applicable Canada Apo-clomipramine Tablet 10 mg Oral Apotex Corporation 1993-12-31 Not applicable Canada Apo-clomipramine Tablet 25 mg Oral Apotex Corporation 1993-12-31 Not applicable Canada
Categories
- ATC Codes
- N06AA04 — Clomipramine
- Drug Categories
- Agents that produce hypertension
- Agents that reduce seizure threshold
- Antidepressive Agents
- Antidepressive Agents Indicated for Depression
- Antidepressive Agents, Tricyclic
- Central Nervous System Agents
- Central Nervous System Depressants
- Combined Inhibitors of Serotonin/Norepinephrine Reuptake
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors (strong)
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Dibenzazepines
- Drugs that are Mainly Renally Excreted
- Heterocyclic Compounds, Fused-Ring
- Hypotensive Agents
- Membrane Transport Modulators
- Moderate Risk QTc-Prolonging Agents
- Narrow Therapeutic Index Drugs
- Nervous System
- Neurotoxic agents
- Neurotransmitter Agents
- Neurotransmitter Uptake Inhibitors
- Non-Selective Monoamine Reuptake Inhibitors
- P-glycoprotein inhibitors
- Psychoanaleptics
- Psychotropic Drugs
- QTc Prolonging Agents
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin 5-HT2A Receptor Antagonists
- Serotonin 5-HT2C Receptor Antagonists
- Serotonin Agents
- Serotonin Modulators
- Serotonin Receptor Antagonists
- Tertiary amine tricyclic antidepressants
- Tricyclics and Other Norepinephrine-reuptake Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as dibenzazepines. These 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.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Benzazepines
- Sub Class
- Dibenzazepines
- Direct Parent
- Dibenzazepines
- Alternative Parents
- Alkyldiarylamines / Azepines / Benzenoids / Aryl chlorides / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives
- Substituents
- Alkyldiarylamine / Amine / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Azepine / Benzenoid / Dibenzazepine / Hydrocarbon derivative
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- dibenzoazepine (CHEBI:47780)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- NUV44L116D
- CAS number
- 303-49-1
- InChI Key
- 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-{14-chloro-2-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,12,14-hexaen-2-yl}propyl)dimethylamine
- SMILES
- CN(C)CCCN1C2=CC=CC=C2CCC2=C1C=C(Cl)C=C2
References
- Synthesis Reference
Schindler, W. and Dietrich, H.; US. Patent 3,515,785; June 2,1970; assigned to Geigy Chemical Corp.
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0015372
- KEGG Drug
- D00811
- KEGG Compound
- C06918
- PubChem Compound
- 2801
- PubChem Substance
- 46505157
- ChemSpider
- 2699
- BindingDB
- 77970
- 2597
- ChEBI
- 47780
- ChEMBL
- CHEMBL415
- ZINC
- ZINC000000020248
- Therapeutic Targets Database
- DAP000742
- PharmGKB
- PA449048
- Guide to Pharmacology
- GtP Drug Page
- PDBe Ligand
- CXX
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Clomipramine
- PDB Entries
- 2q6h / 2qei / 4mma / 6g9i
- FDA label
- Download (712 KB)
- MSDS
- Download (74.2 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Obsessive Compulsive Disorder (OCD) 1 somestatus stop reason just information to hide Not Available Completed Basic Science Major Depressive Disorder (MDD) 1 somestatus stop reason just information to hide Not Available Completed Treatment Depression 1 somestatus stop reason just information to hide Not Available Unknown Status Treatment Major depressive disorder, recurrent episode 1 somestatus stop reason just information to hide 4 Completed Treatment Obsessive Compulsive Disorder (OCD) 2 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Abic Ltd.
- Basel Pharmaceuticals Div Ciba Geigy Corp.
- Comprehensive Consultant Services Inc.
- Dispensing Solutions
- Gallipot
- Heartland Repack Services LLC
- Mallinckrodt Inc.
- Murfreesboro Pharmaceutical Nursing Supply
- Mylan
- Novartis AG
- Novopharm Ltd.
- Nucare Pharmaceuticals Inc.
- Patheon Inc.
- Pharmaceutical Utilization Management Program VA Inc.
- Pharmacy Service Center
- Physicians Total Care Inc.
- Preferred Pharmaceuticals Inc.
- Remedy Repack
- Sandoz
- Taro Pharmaceuticals USA
- Teva Pharmaceutical Industries Ltd.
- Dosage Forms
Form Route Strength Injection, solution Intramuscular; Intravenous 25 MG/2ML Tablet, sugar coated Oral Tablet, coated Oral 10 MG Tablet, extended release Oral 75 MG Injection, solution Intramuscular; Intravenous Tablet, film coated Oral Tablet, film coated Oral 75 mg Tablet, film coated Oral 25 mg Tablet, sugar coated Oral 25 mg Tablet, film coated Oral 10 MG Tablet, extended release Oral 75 mg/1 Tablet, extended release Oral Capsule Oral 25 mg/1 Capsule Oral 50 mg/1 Capsule Oral 75 mg/1 Tablet Oral 25 mg Tablet Oral 10 mg Tablet Oral 50 mg Capsule Oral 50 mg Tablet Oral 10 mg / tab Tablet Oral 25 mg / tab Tablet Oral 50 mg / tab Tablet, coated Oral 25 mg Capsule Oral 10 mg Capsule Oral 25 mg - Prices
Unit description Cost Unit Clomipramine hcl powder 17.88USD g Anafranil 25 mg capsule 13.51USD capsule Anafranil 50 mg capsule 13.51USD capsule Anafranil 75 mg capsule 13.24USD capsule ClomiPRAMINE HCl 75 mg capsule 1.55USD capsule Clomipramine 75 mg capsule 1.33USD capsule Clomipramine 50 mg capsule 1.01USD capsule ClomiPRAMINE HCl 25 mg capsule 0.88USD capsule Anafranil 50 mg Tablet 0.77USD tablet Clomipramine 25 mg capsule 0.75USD capsule ClomiPRAMINE HCl 50 mg capsule 0.57USD capsule Apo-Clomipramine 50 mg Tablet 0.43USD tablet Co Clomipramine 50 mg Tablet 0.43USD tablet Anafranil 25 mg Tablet 0.42USD tablet Anafranil 10 mg Tablet 0.31USD tablet Apo-Clomipramine 25 mg Tablet 0.23USD tablet Co Clomipramine 25 mg Tablet 0.23USD tablet Apo-Clomipramine 10 mg Tablet 0.17USD tablet Co Clomipramine 10 mg Tablet 0.17USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 191.5-192 Schindler, W. and Dietrich, H.; US. Patent 3,515,785; June 2,1970; assigned to Geigy Chemical Corp. boiling point (°C) 160-170 °C at 3.00E-01 mm Hg PhysProp water solubility 0.294 mg/L Not Available logP 5.19 HANSCH,C ET AL. (1995) - Predicted Properties
Property Value Source Water Solubility 0.0144 mg/mL ALOGPS logP 5.04 ALOGPS logP 4.88 Chemaxon logS -4.3 ALOGPS pKa (Strongest Basic) 9.2 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 6.48 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 95.41 m3·mol-1 Chemaxon Polarizability 35.73 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule Yes Chemaxon MDDR-like Rule No Chemaxon - 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 inhibitor Non-inhibitor 0.9176 CYP450 2D6 inhibitor Inhibitor 0.8932 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 177.66154 predictedDarkChem Lite v0.1.0 [M-H]- 167.96239 predictedDeepCCS 1.0 (2019) [M+H]+ 178.16554 predictedDarkChem Lite v0.1.0 [M+H]+ 170.32039 predictedDeepCCS 1.0 (2019) [M+Na]+ 177.92944 predictedDarkChem Lite v0.1.0 [M+Na]+ 176.41353 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion and possibly one proton in an overall electroneutral transport cycle. Transports serotonin across the plasma membrane from the extracellular compartment to the cytosol thus limiting serotonin intercellular signaling (PubMed:10407194, PubMed:12869649, PubMed:21730057, PubMed:27049939, PubMed:27756841, PubMed:34851672). Essential for serotonin homeostasis in the central nervous system. In the developing somatosensory cortex, acts in glutamatergic neurons to control serotonin uptake and its trophic functions accounting for proper spatial organization of cortical neurons and elaboration of sensory circuits. In the mature cortex, acts primarily in brainstem raphe neurons to mediate serotonin uptake from the synaptic cleft back into the pre-synaptic terminal thus terminating serotonin signaling at the synapse (By similarity). Modulates mucosal serotonin levels in the gastrointestinal tract through uptake and clearance of serotonin in enterocytes. Required for enteric neurogenesis and gastrointestinal reflexes (By similarity). Regulates blood serotonin levels by ensuring rapid high affinity uptake of serotonin from plasma to platelets, where it is further stored in dense granules via vesicular monoamine transporters and then released upon stimulation (PubMed:17506858, PubMed:18317590). Mechanistically, the transport cycle starts with an outward-open conformation having Na1(+) and Cl(-) sites occupied. The binding of a second extracellular Na2(+) ion and serotonin substrate leads to structural changes to outward-occluded to inward-occluded to inward-open, where the Na2(+) ion and serotonin are released into the cytosol. Binding of intracellular K(+) ion induces conformational transitions to inward-occluded to outward-open and completes the cycle by releasing K(+) possibly together with a proton bound to Asp-98 into the extracellular compartment. Na1(+) and Cl(-) ions remain bound throughout the transport cycle (PubMed:10407194, PubMed:12869649, PubMed:21730057, PubMed:27049939, PubMed:27756841, PubMed:34851672). Additionally, displays serotonin-induced channel-like conductance for monovalent cations, mainly Na(+) ions. The channel activity is uncoupled from the transport cycle and may contribute to the membrane resting potential or excitability (By similarity)
- Specific Function
- actin filament binding
- Gene Name
- SLC6A4
- Uniprot ID
- P31645
- Uniprot Name
- Sodium-dependent serotonin transporter
- Molecular Weight
- 70324.165 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:1330647, PubMed:18703043, PubMed:19057895, PubMed:21645528, PubMed:22300836, PubMed:35084960, PubMed:38552625). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD) (PubMed:28129538, PubMed:35084960). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:28129538, PubMed:35084960). HTR2A is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers that modulate the activity of phosphatidylinositol 3-kinase and promote the release of Ca(2+) ions from intracellular stores, respectively (PubMed:18703043, PubMed:28129538, PubMed:35084960). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:28129538, PubMed:35084960). Affects neural activity, perception, cognition and mood (PubMed:18297054). Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction (By similarity)
- Specific Function
- 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding
- Gene Name
- HTR2A
- Uniprot ID
- P28223
- Uniprot Name
- 5-hydroxytryptamine receptor 2A
- Molecular Weight
- 52602.58 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:18703043, PubMed:23519210, PubMed:7926008, PubMed:8078486, PubMed:8143856, PubMed:8882600). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances (PubMed:12970106, PubMed:18703043, PubMed:23519210, PubMed:23519215, PubMed:24357322, PubMed:28129538, PubMed:30127358, PubMed:36087581, PubMed:7926008, PubMed:8078486, PubMed:8143856). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:23519215, PubMed:28129538, PubMed:8078486, PubMed:8143856, PubMed:8882600). HTR2B is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers that modulate the activity of phosphatidylinositol 3-kinase and promote the release of Ca(2+) ions from intracellular stores, respectively (PubMed:18703043, PubMed:23519215, PubMed:28129538, PubMed:30127358, PubMed:36087581, PubMed:8078486, PubMed:8143856, PubMed:8882600). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:23519215, PubMed:28129538, PubMed:30127358, PubMed:36087581). Plays a role in the regulation of dopamine and 5-hydroxytryptamine release, 5-hydroxytryptamine uptake and in the regulation of extracellular dopamine and 5-hydroxytryptamine levels, and thereby affects neural activity. May play a role in the perception of pain (By similarity). Plays a role in the regulation of behavior, including impulsive behavior (PubMed:21179162). Required for normal proliferation of embryonic cardiac myocytes and normal heart development (By similarity). Protects cardiomyocytes against apoptosis (By similarity). Plays a role in the adaptation of pulmonary arteries to chronic hypoxia (By similarity). Plays a role in vasoconstriction (By similarity). Required for normal osteoblast function and proliferation, and for maintaining normal bone density (By similarity). Required for normal proliferation of the interstitial cells of Cajal in the intestine (By similarity)
- Specific Function
- G protein-coupled serotonin receptor activity
- Gene Name
- HTR2B
- Uniprot ID
- P41595
- Uniprot Name
- 5-hydroxytryptamine receptor 2B
- Molecular Weight
- 54297.41 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:12970106, PubMed:18703043, PubMed:19057895, PubMed:29398112, PubMed:7895773). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD) (PubMed:19057895, PubMed:29398112). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:18703043, PubMed:29398112). HTR2C is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers that modulate the activity of phosphatidylinositol 3-kinase and promote the release of Ca(2+) ions from intracellular stores, respectively (PubMed:18703043, PubMed:29398112). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:29398112). Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelanocortin neurons and the release of CRH that then regulates the release of corticosterone (By similarity). Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress (By similarity). Plays a role in insulin sensitivity and glucose homeostasis (By similarity)
- Specific Function
- 1-(4-iodo-2,5-dimethoxyphenyl)propan-2-amine binding
- Gene Name
- HTR2C
- Uniprot ID
- P28335
- Uniprot Name
- 5-hydroxytryptamine receptor 2C
- Molecular Weight
- 51804.645 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline) (PubMed:2008212, PubMed:8125921). Can also mediate sodium- and chloride-dependent transport of dopamine (PubMed:11093780, PubMed:8125921)
- Specific Function
- actin binding
- Gene Name
- SLC6A2
- Uniprot ID
- P23975
- Uniprot Name
- Sodium-dependent noradrenaline transporter
- Molecular Weight
- 69331.42 Da
References
- 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. [Article]
- Jungkun G, Kuss HJ, Gsell W: Long-term effects of tricyclic antidepressants on norepinephrine kinetics in humans. J Neural Transm (Vienna). 2001;108(3):349-62. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2) (PubMed:9084911). Participates in the formation of novel hepoxilin regioisomers (PubMed:21046276). Negatively regulates CDK5 activity via p25/p35 translocation to prevent neurodegeneration
- Specific Function
- dinitrosyl-iron complex binding
- Gene Name
- GSTP1
- Uniprot ID
- P09211
- Uniprot Name
- Glutathione S-transferase P
- Molecular Weight
- 23355.625 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55944.565 Da
References
- Brown JT, Schneiderhan M, Eum S, Bishop JR: Serum clomipramine and desmethylclomipramine levels in a CYP2C19 and CYP2D6 intermediate metabolizer. Pharmacogenomics. 2017 May;18(7):601-605. doi: 10.2217/pgs-2017-0015. Epub 2017 May 4. [Article]
- Yokono A, Morita S, Someya T, Hirokane G, Okawa M, Shimoda K: The effect of CYP2C19 and CYP2D6 genotypes on the metabolism of clomipramine in Japanese psychiatric patients. J Clin Psychopharmacol. 2001 Dec;21(6):549-55. [Article]
- Flockhart Table of Drug Interactions [Link]
- The P450 Program [Link]
- Cytochrome P450 Interactions [File]
- Clomipramine FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
- Specific Function
- aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 Da
References
- Fisman S, Reniers D, Diaz P: Erythromycin interaction with risperidone or clomipramine in an adolescent. J Child Adolesc Psychopharmacol. 1996 Summer;6(2):133-8. doi: 10.1089/cap.1996.6.133. [Article]
- Nielsen KK, Flinois JP, Beaune P, Brosen K: The biotransformation of clomipramine in vitro, identification of the cytochrome P450s responsible for the separate metabolic pathways. J Pharmacol Exp Ther. 1996 Jun;277(3):1659-64. [Article]
- Flockhart Table of Drug Interactions [Link]
- PDR, Anafranil [Link]
- Clomipramine FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Nielsen KK, Flinois JP, Beaune P, Brosen K: The biotransformation of clomipramine in vitro, identification of the cytochrome P450s responsible for the separate metabolic pathways. J Pharmacol Exp Ther. 1996 Jun;277(3):1659-64. [Article]
- Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [Article]
- The P450 Program [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- 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. [Article]
- Schrickx JA, Fink-Gremmels J: Inhibition of P-glycoprotein by psychotherapeutic drugs in a canine cell model. J Vet Pharmacol Ther. 2014 Oct;37(5):515-7. doi: 10.1111/jvp.12111. Epub 2014 Mar 7. [Article]
Drug created at June 13, 2005 13:24 / Updated at November 01, 2024 00:04