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Identification
- Summary
Doxepin is a psychotropic agent used for the treatment of depression, anxiety, manic-depressive disorder, and insomnia.
- Brand Names
- Prudoxin, Silenor, Sinequan, Zonalon
- Generic Name
- Doxepin
- DrugBank Accession Number
- DB01142
- Background
Doxepin is a psychotropic agent with antidepressant and anxiolytic properties.9 It is a tertiary amine that can be presented as (E) and (Z) stereoisomers with the (Z) stereoisomer corresponding to cidoxepin. Doxepin commonly produces a 5:1 (E):(Z) racemic mixture.8
In a strict sense, doxepin is not a tricyclic antidepressant but it is commonly associated with the class since it shares a lot of properties with members of the drug family including amitriptyline, clomipramine, desipramine, imipramine, nortriptyline, protriptyline and trimipramine.13
Doxepin was developed by Pfizer and FDA approved in 1969 as an antidepressant.11 However, in 2010 it was approved for the treatment of insomnia. The latter indication was presented by Pernix Therapeutics.12
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Doxepin (DB01142)
- Weight
- Average: 279.3761
Monoisotopic: 279.162314299 - Chemical Formula
- C19H21NO
- Synonyms
- Doxepin
- Doxepina
- Doxepinum
- External IDs
- MF 10
Pharmacology
- Indication
Oral doxepin is approved for the following indications:
- Treatment of depression and/or anxiety.1
- Treatment of depression and/or anxiety associated with different conditions, including alcoholism, organic disease and manic-depressive disorders.7
- Treatment of psychotic depressive disorders with associated anxiety.7
- Treatment of involutional depression.7
- Treatment of manic-depressive disorder.7
- Treatment of insomnia characterized by difficulties with sleep maintenance.1
Topical doxepin is also approved for short-term (up to 8 days) management of moderate pruritus in adult patients with atopic dermatitis, pruritus or lichen simplex chronicus.7
Off-label, doxepin is used topically for the management of neuropathic pain.2
Depression is a common medical illness that causes feelings of sadness and or loss of interest in prior enjoyable activities. This condition can lead to emotional and physical disturbances that can decrease the ability of a person to function in a regular environment.14
Anxiety is a normal reaction of the body towards a normal danger. When the anxious state is exacerbated or appears on situations without danger, it is defined as an anxiety disorder. This disorders can appear in different forms such as phobias, panic, obsessive-compulsive disorder and post-traumatic stress disorder.15
Insomnia is a sleep disorder that directly affects the quality of life of the individual. It is characterized by the complication either to fall asleep or to stay asleep. This condition can be occasional or chronic.16
Pruritus is defined as an unpleasant skin reaction that provokes the urge to scratch. It can be localized or generalized and it can appear in an acute or chronic manner.17
Neuropathic pain occurs due to the damage or dysfunction of the peripheral or central nervous system rather than stimulation of the pain receptors.18
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Anxiety •••••••••••• •••••••• •••••• Treatment of Anxiety •••••••••••• Treatment of Depression •••••••••••• •••••••• •••••• Treatment of Depression •••••••••••• •••••••• •••••• Treatment of Insomnia •••••••••••• - Contraindications & Blackbox Warnings
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Similar to other tricyclic antidepressants, doxepin was shown, in preclinical trials, to decrease the electrical activity of the brain, prolong the hexobarbital-induced sleep and block avoidance behavior without affecting the conditioned emotional response. At high doses, it also produces symptoms of central nervous system depression.20
Doxepin is known to cause antidepressant, sedative, and anticholinergic effects. At high doses, its anticholinergic and antiadrenergic properties are the most prevalent which limit its efficacy. These effects are observed at high doses where its affinity for H1 histamine receptor is lost and its binding to other receptors is observed.1
The maximal antidepressive effects of doxepin are present around two weeks following initiation of therapy.6 However, the sedative effects of doxepin, usually used for the treatment of insomnia or anxiety, are observed immediately after administration.7
- Mechanism of action
Doxepin exact mechanism of action is not very clear. However, doxepin is known to be a selective histamine H1 receptor blocker.1 This effect on histamine receptors indicates effectiveness in skin conditions.7
Breaking its function according to the different effect, doxepin's antidepressive action is primarily associated with the inhibition of the central nervous system biogenic amine reuptake; more specifically, norepinephrine and serotonin at synaptic nerve terminals. This effect increases the level of monoamines in the synaptic site which in order increases the activity at the post-synaptic neuron receptor sites.6 It has been suggested that doxepin also desensitizes both serotonin 1A receptors and beta-adrenergic receptors.7
It is known that the lack of dopamine transporters in the frontal cortex and the transmission of dopamine in this region is largely inactivated by the effect of norepinephrine reuptake. Hence, doxepin action on the frontal cortex is suggested to increase dopamine neurotransmission in this area.7
Target Actions Organism AHistamine H1 receptor antagonistHumans AHistamine H2 receptor antagonistHumans ASodium-dependent noradrenaline transporter inhibitorHumans ASodium-dependent serotonin transporter inhibitorHumans U5-hydroxytryptamine receptor 2A antagonistHumans U5-hydroxytryptamine receptor 2B antagonistHumans U5-hydroxytryptamine receptor 2C antagonistHumans UMuscarinic acetylcholine receptor M1 antagonistHumans UMuscarinic acetylcholine receptor M2 antagonistHumans UMuscarinic acetylcholine receptor M3 antagonistHumans UMuscarinic acetylcholine receptor M4 antagonistHumans UMuscarinic acetylcholine receptor M5 antagonistHumans UAlpha-1A adrenergic receptor antagonistHumans UAlpha-1B adrenergic receptor antagonistHumans UAlpha-1D adrenergic receptor antagonistHumans U5-hydroxytryptamine receptor 1A antagonistHumans U5-hydroxytryptamine receptor 6 binderHumans UHistamine H4 receptor binderHumans UPotassium voltage-gated channel subfamily H member 2 inhibitorHumans - Absorption
Doxepin is moderately absorbed following oral ingestion with a bioavailability of 30%.6 The median peak concentration of doxepin ranges from 8.8-45.8 ng/ml and it is achieved 3.5 hours after initial administration. Its absorption is increased with concomitant administration of a high-fat meal.19
- Volume of distribution
The mean apparent volume of distribution of doxepin is reported to be of 20 L/kg.6
- Protein binding
Equilibrium dialysis indicates a mean protein binding of 75.5% for doxepin and 76% for desmethyldoxepin.3
- Metabolism
Doxepin is extensively metabolized to N-desmethyldoxepin which is a biologically active metabolite and other inactive metabolites.2 The first-pass metabolism accounts for 55-87% of the administered dose.5 After, the secondary metabolism is driven by the transformation of N-desmethyldoxepin to its glucuronide conjugates.19
The main metabolic enzymes involved in the transformation of doxepin are the members of the cytochrome P450 family, CYP2C19 and CYP2D6 with minor involvement of CYP1A2 and CYP2C9.19
Hover over products below to view reaction partners
- Route of elimination
The elimination profile of doxepin is presented as biphasic.3 It is excreted in the urine mainly in the form of glucuronide conjugates. Less than 3% of a doxepin dose is excreted in the urine as parent compound or nordoxepin.10
- Half-life
The mean elimination half-life is reported to be of 15 hours.6
- Clearance
The mean total apparent plasma clearance of a single oral dose of 50 mg doxepin in healthy individuals is 0.93 l/hr/kg.3
- Adverse Effects
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Oral LD50 values of doxepin in mouse and rat are 180 mg/kg and 147 mg/kg, respectively.MSDS In an overdose state, symptoms of convulsions, dysrhythmias, coma, severe hypotension, central nervous system depression, changes on electrocardiography results and death have been observed.7
On fertility studies, doxepin was shown to increase the copulatory interval, decrease the corpora lutea, decrease implantation, decreased the number of viable embryos, decrease litter size, increase the number of abnormal sperm and decrease the sperm motility. There is no evidence indicating carcinogenic and mutagenic potential.Label
- Pathways
Pathway Category Doxepin H1-Antihistamine Action Drug action Doxepin 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*3 Not Available 2549delA Effect Directly Studied The presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of doxepin. 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 doxepin. 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 doxepin. 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 doxepin. 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 doxepin. 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 doxepin. Details Cytochrome P450 2D6 CYP2D6*7 Not Available 2935A>C Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, 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, 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, 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, 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, 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, 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, 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, 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, dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*21 Not Available 2573insC Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, 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, 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, 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, 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, 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, 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, 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, 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, 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, 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, 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, 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, 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, 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, dose reduction recommended. Details Cytochrome P450 2D6 CYP2D6*92 Not Available 1995delC Effect Inferred Poor drug metabolizer. For individual with two non-functional alleles, 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, 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, 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 G allele Effect Directly Studied The presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of doxepin. 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 doxepin. 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 Doxepin is combined with 1,2-Benzodiazepine. Abacavir Abacavir may decrease the excretion rate of Doxepin which could result in a higher serum level. Abametapir The serum concentration of Doxepin can be increased when it is combined with Abametapir. Abatacept The metabolism of Doxepin can be increased when combined with Abatacept. Abiraterone The serum concentration of Doxepin can be increased when it is combined with Abiraterone. - Food Interactions
- Avoid alcohol. Co-administration may enhance CNS adverse effects such as drowsiness and sedation.
- Avoid St. John's Wort. Co-administration may lead to decreased serum concentrations of doxepin.
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 Doxepin hydrochloride 3U9A0FE9N5 1229-29-4 MHNSPTUQQIYJOT-UHFFFAOYSA-N - Product Images
- International/Other Brands
- Adapin (PennwaIt) / Aponal (Pfizer) / Doxepine (Shou Chan) / Quitaxon (Lexphar)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Doxepin Capsule 75 mg Oral Aa Pharma Inc 1993-12-31 Not applicable Canada 
Doxepin Capsule 150 mg Oral Aa Pharma Inc 1993-12-31 Not applicable Canada Doxepin Capsule 50 mg Oral Aa Pharma Inc 1993-12-31 Not applicable Canada Doxepin Capsule 10 mg Oral Aa Pharma Inc 1993-12-31 Not applicable Canada Doxepin Capsule 100 mg Oral Aa Pharma Inc 1993-12-31 Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Alti-doxepin - Cap 10mg Capsule 10 mg / cap Oral Altimed Pharma Inc. 1995-12-31 2005-05-27 Canada Alti-doxepin-cap 25mg Capsule 25 mg / cap Oral Altimed Pharma Inc. 1995-12-31 2005-05-27 Canada Alti-doxepin-cap 50mg Capsule 50 mg / cap Oral Altimed Pharma Inc. 1995-12-31 2005-05-27 Canada Alti-doxepin-cap 75mg Capsule 75 mg / cap Oral Altimed Pharma Inc. 1995-12-31 2005-05-27 Canada Doxepin Tablet 6 mg/1 Oral Ajanta Pharma USA Inc. 2024-07-01 Not applicable US 
Categories
- ATC Codes
- N06AA12 — Doxepin
- N06AA — Non-selective monoamine reuptake inhibitors
- N06A — ANTIDEPRESSANTS
- N06 — PSYCHOANALEPTICS
- N — NERVOUS SYSTEM
- Drug Categories
- Acid Reducers
- Adrenergic alpha-1 Receptor Antagonists
- Adrenergic alpha-Antagonists
- Adrenergic Antagonists
- Agents producing tachycardia
- Agents that produce hypertension
- Agents that reduce seizure threshold
- Anticholinergic Agents
- Antidepressive Agents
- Antidepressive Agents Indicated for Depression
- Antidepressive Agents, Tricyclic
- Antipruritics and Local Anesthetics
- Antipruritics, Incl. Antihistamines, Anesthetics, Etc.
- Central Nervous System Agents
- Central Nervous System Depressants
- Combined Inhibitors of Serotonin/Norepinephrine Reuptake
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Dermatologicals
- Dibenzoxepins
- Drugs that are Mainly Renally Excreted
- Ethers, Cyclic
- Heterocyclic Compounds, Fused-Ring
- Histamine Agents
- Histamine Antagonists
- Histamine H1 Antagonists
- Histamine H2 Antagonists
- Hypnotics and Sedatives
- Muscarinic Antagonists
- Nervous System
- Neurotoxic agents
- Neurotransmitter Agents
- Non-Selective Monoamine Reuptake Inhibitors
- P-glycoprotein substrates
- Potential QTc-Prolonging Agents
- Psychoanaleptics
- Psychotropic Drugs
- QTc Prolonging Agents
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin 5-HT1 Receptor Antagonists
- Serotonin 5-HT1A Receptor Antagonists
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin 5-HT2A Receptor Antagonists
- Serotonin 5-HT2C Receptor Antagonists
- Serotonin Agents
- Serotonin Modulators
- Serotonin Receptor Antagonists
- Sleep Aids, Pharmaceutical
- 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 dibenzoxepines. These are compounds containing a dibenzoxepine moiety, which consists of two benzene connected by an oxazepine ring.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Benzoxepines
- Sub Class
- Dibenzoxepines
- Direct Parent
- Dibenzoxepines
- Alternative Parents
- Alkyl aryl ethers / Benzenoids / Trialkylamines / Oxacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- Alkyl aryl ether / Amine / Aromatic heteropolycyclic compound / Benzenoid / Dibenzoxepine / Ether / Hydrocarbon derivative / Organic nitrogen compound / Organic oxygen compound / Organonitrogen compound
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- tertiary amino compound, dibenzooxepine (CHEBI:4710)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 5ASJ6HUZ7D
- CAS number
- 1668-19-5
- InChI Key
- ODQWQRRAPPTVAG-UHFFFAOYSA-N
- InChI
- InChI=1S/C19H21NO/c1-20(2)13-7-11-17-16-9-4-3-8-15(16)14-21-19-12-6-5-10-18(17)19/h3-6,8-12H,7,13-14H2,1-2H3
- IUPAC Name
- dimethyl(3-{9-oxatricyclo[9.4.0.0^{3,8}]pentadeca-1(15),3,5,7,11,13-hexaen-2-ylidene}propyl)amine
- SMILES
- [H]C(CCN(C)C)=C1C2=CC=CC=C2COC2=CC=CC=C12
References
- Synthesis Reference
- US20090074862
- General References
- Rojas-Fernandez CH, Chen Y: Use of ultra-low-dose (Article]
- Authors unspecified: Doxepin . [Article]
- Virtanen R, Scheinin M, Iisalo E: Single dose pharmacokinetics of doxepin in healthy volunteers. Acta Pharmacol Toxicol (Copenh). 1980 Nov;47(5):371-6. [Article]
- Singh H, Becker PM: Novel therapeutic usage of low-dose doxepin hydrochloride. Expert Opin Investig Drugs. 2007 Aug;16(8):1295-305. [Article]
- Negrusz A, Moore CM, Perry JL: Detection of doxepin and its major metabolite desmethyldoxepin in hair following drug therapy. J Anal Toxicol. 1998 Oct;22(6):531-6. [Article]
- Pagliaro L. and Pagliaro A. (1999). Psychologists' psychotropic drug reference. Taylor and Francis.
- Stephen M. Stahl (2006). Essential Psychopharmacology: The Prescriber's Guide: Revised and Updated Edition. Cambridge University Press. [ISBN:9780521683500]
- Elks J. and Ganellin C.R. (1990). The dictionary of drugs. Springer Science.
- Bishop M. (2015). Clinical chemistry: techniques, principles and correlations (6th ed.). Content Technologies Inc. [ISBN:978-146-7263-085]
- FDA Label: SilenorTM (doxepin) tablets for oral administration [Link]
- FDA approvals [Link]
- FDA approvals [Link]
- Encyclopedia [Link]
- American Psychiatric Association [Link]
- Canadian Mental Health Association [Link]
- HealthLink BC [Link]
- Cleveland Clinic [Link]
- Merck Manuals [Link]
- Dehli Psychiatry Journal paper [Link]
- Novo-doxepin product monograph [Link]
- External Links
- Human Metabolome Database
- HMDB0015273
- KEGG Drug
- D07875
- KEGG Compound
- C06971
- PubChem Compound
- 667468
- PubChem Substance
- 46505232
- ChemSpider
- 3046
- BindingDB
- 50225488
- 3638
- ChEBI
- 4710
- ChEMBL
- CHEMBL1628227
- Therapeutic Targets Database
- DAP000177
- PharmGKB
- PA449409
- Guide to Pharmacology
- GtP Drug Page
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Doxepin
- PDB Entries
- 3rze
- FDA label
- Download (128 KB)
- MSDS
- Download (585 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 Basic Science Pruritus 2 somestatus stop reason just information to hide Not Available Recruiting Supportive Care Swallowing-induced Pain 1 somestatus stop reason just information to hide Not Available Terminated Not Available Bipolar Disorder (BD) 1 somestatus stop reason just information to hide Not Available Unknown Status Treatment Dyspepsia / Functional Gastrointestinal Disorders (FGID) / Psychosomatic Disorders 1 somestatus stop reason just information to hide Not Available Withdrawn Basic Science Pruritus 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Advanced Pharmaceutical Services Inc.
- Amerisource Health Services Corp.
- A-S Medication Solutions LLC
- Bioglan Pharmaceuticals Co.
- Coupler Enterprises Inc.
- Direct Dispensing Inc.
- Dispensing Solutions
- Diversified Healthcare Services Inc.
- DPT Laboratories Ltd.
- Healthpoint Ltd.
- Heartland Repack Services LLC
- Innoviant Pharmacy Inc.
- Lederle Arzneimittel Cyanamid GmbH
- Liberty Pharmaceuticals
- Major Pharmaceuticals
- Medisca Inc.
- Murfreesboro Pharmaceutical Nursing Supply
- Mylan
- Nucare Pharmaceuticals Inc.
- Par Pharmaceuticals
- PCA LLC
- PD-Rx Pharmaceuticals Inc.
- Pfizer Inc.
- Pharmaceutical Utilization Management Program VA Inc.
- Pharmaderm
- Pharmedix
- Physicians Total Care Inc.
- Preferred Pharmaceuticals Inc.
- Prepackage Specialists
- Prepak Systems Inc.
- Prescript Pharmaceuticals
- Qualitest
- Rebel Distributors Corp.
- Remedy Repack
- Silarx Pharmaceuticals
- Southwood Pharmaceuticals
- Stat Rx Usa
- Teva Pharmaceutical Industries Ltd.
- UDL Laboratories
- United Research Laboratories Inc.
- Watson Pharmaceuticals
- Wockhardt Ltd.
- Dosage Forms
Form Route Strength Cream Topical 5 % Capsule Oral 10 mg Capsule Oral 25 mg Capsule Oral 50 mg Solution Oral 11.31 mg Tablet, film coated Oral 100 MG Tablet, film coated Oral 10 MG Tablet, film coated Oral 25 MG Tablet, film coated Oral 50 MG Tablet, film coated Oral 75 MG Tablet, film coated Oral 3 mg/1 Tablet, film coated Oral 6 mg/1 Tablet, film coated Oral 10 mg/1 Tablet, film coated Oral 100 mg/1 Tablet, film coated Oral 25 mg/1 Tablet, film coated Oral 50 mg/1 Tablet, film coated Oral 75 mg/1 Capsule Oral 10 mg/1 Capsule Oral 100 mg/1 Capsule Oral 150 mg/1 Capsule Oral 25 mg/1 Capsule Oral 50 mg/1 Capsule Oral 75 mg/1 Solution Oral 10 mg/1mL Tablet Oral 3 mg/1 Tablet Oral 6 mg/1 Solution Oral 40 mg/mL Capsule Oral 150 mg / cap Tablet, coated Oral 50 mg Tablet Oral 56.53 mg Capsule Oral 150 mg Capsule Oral 100 mg Capsule Oral 75 mg Tablet Oral 3.00 mg Tablet Oral 6.00 mg Solution, concentrate Oral 10 mg/1mL Capsule Oral 100 mg / cap Capsule Oral 10 mg / cap Capsule Oral 25 mg / cap Capsule Oral 50 mg / cap Capsule Oral 75 mg / cap Cream Topical 50 mg/1g Cream Topical 5 % w/w - Prices
Unit description Cost Unit Zonalon 5% Cream 45 gm Tube 190.13USD tube Zonalon 5% Cream 30 gm Tube 144.29USD tube Doxepin hcl powder 8.88USD g Doxepin 150 mg capsule 3.33USD capsule Prudoxin 5% cream 3.05USD g Sinequan 100 mg Capsule 1.22USD capsule Novo-Doxepin 150 mg Capsule 1.18USD capsule Sinequan 75 mg Capsule 0.93USD capsule Zonalon 5% cream 0.89USD g Doxepin HCl 150 mg capsule 0.87USD capsule Apo-Doxepin 100 mg Capsule 0.68USD capsule Novo-Doxepin 100 mg Capsule 0.68USD capsule Sinequan 50 mg Capsule 0.64USD capsule Doxepin 50 mg capsule 0.57USD capsule Doxepin HCl 100 mg capsule 0.56USD capsule Novo-Doxepin 75 mg Capsule 0.52USD capsule Apo-Doxepin 75 mg Capsule 0.52USD capsule Doxepin HCl 75 mg capsule 0.43USD capsule Apo-Doxepin 50 mg Capsule 0.36USD capsule Novo-Doxepin 50 mg Capsule 0.36USD capsule Sinequan 25 mg Capsule 0.35USD capsule Doxepin 10 mg capsule 0.32USD capsule Sinequan 10 mg Capsule 0.28USD capsule Doxepin HCl 50 mg capsule 0.25USD capsule Doxepin HCl 25 mg capsule 0.23USD capsule Doxepin 75 mg capsule 0.21USD capsule Doxepin HCl 10 mg capsule 0.21USD capsule Apo-Doxepin 10 mg Capsule 0.2USD capsule Apo-Doxepin 25 mg Capsule 0.19USD capsule Novo-Doxepin 25 mg Capsule 0.19USD capsule Doxepin 25 mg capsule 0.18USD capsule Doxepin 100 mg capsule 0.14USD capsule Doxepin HCl 10 mg/ml Concentrate 0.13USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US6211229 No 2001-04-03 2020-02-17 US US9107898 No 2015-08-18 2028-05-01 US US8513299 No 2013-08-20 2030-04-14 US US7915307 No 2011-03-29 2027-08-24 US US9532971 No 2017-01-03 2029-06-01 US US9486437 No 2016-11-08 2027-05-18 US US9572814 No 2017-02-21 2027-07-20 US US9861607 No 2018-01-09 2027-05-18 US US9907780 No 2018-03-06 2028-04-11 US US10238620 No 2019-03-26 2027-05-18 US US10548871 No 2020-02-04 2028-04-11 US US10653660 No 2020-05-19 2027-07-20 US US10653662 No 2020-05-19 2027-05-18 US US11110074 No 2021-09-07 2027-07-20 US US11096920 No 2021-08-24 2028-04-11 US US11234954 No 2008-01-18 2028-01-18 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 185-191 ºC 'MSDS' boiling point (°C) 154-157 ºC at 0.03 mmHg Budavari S. 1996. The Merck Index. water solubility 31.6 mg/L (at 25 °C) Yalkowsky S. et al. 1992. Aquasol Database of Aqueous Solubility. logP 4.29 Maslanka A. et al. 2011. J AOAC Int. pKa 8.96 Embil K. and Torosian G. 1982. J Pharm Sci. - Predicted Properties
Property Value Source Water Solubility 0.0319 mg/mL ALOGPS logP 4.08 ALOGPS logP 3.84 Chemaxon logS -3.9 ALOGPS pKa (Strongest Basic) 9.76 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 12.47 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 98.24 m3·mol-1 Chemaxon Polarizability 32.47 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 + 0.9931 Blood Brain Barrier + 0.9381 Caco-2 permeable + 0.8108 P-glycoprotein substrate Substrate 0.8147 P-glycoprotein inhibitor I Inhibitor 0.8147 P-glycoprotein inhibitor II Inhibitor 0.8214 Renal organic cation transporter Inhibitor 0.7883 CYP450 2C9 substrate Non-substrate 0.7846 CYP450 2D6 substrate Substrate 0.8919 CYP450 3A4 substrate Substrate 0.7475 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Inhibitor 0.8932 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Non-inhibitor 0.917 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6362 Ames test Non AMES toxic 0.9133 Carcinogenicity Non-carcinogens 0.8322 Biodegradation Not ready biodegradable 0.8461 Rat acute toxicity 3.2478 LD50, mol/kg Not applicable hERG inhibition (predictor I) Strong inhibitor 0.5346 hERG inhibition (predictor II) Inhibitor 0.6959
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 179.8014141 predictedDarkChem Lite v0.1.0 [M-H]- 164.4939 predictedDeepCCS 1.0 (2019) [M+H]+ 180.5175141 predictedDarkChem Lite v0.1.0 [M+H]+ 166.8519 predictedDeepCCS 1.0 (2019) [M+Na]+ 179.6873141 predictedDarkChem Lite v0.1.0 [M+Na]+ 172.94505 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- Curator comments
- Ki < 1 nM
- General Function
- In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system
- Specific Function
- G protein-coupled serotonin receptor activity
- Gene Name
- HRH1
- Uniprot ID
- P35367
- Uniprot Name
- Histamine H1 receptor
- Molecular Weight
- 55783.61 Da
References
- Tashiro M, Sakurada Y, Iwabuchi K, Mochizuki H, Kato M, Aoki M, Funaki Y, Itoh M, Iwata R, Wong DF, Yanai K: Central effects of fexofenadine and cetirizine: measurement of psychomotor performance, subjective sleepiness, and brain histamine H1-receptor occupancy using 11C-doxepin positron emission tomography. J Clin Pharmacol. 2004 Aug;44(8):890-900. [Article]
- Tran VT, Lebovitz R, Toll L, Snyder SH: [3H]doxepin interactions with histamine H1-receptors and other sites in guinea pig and rat brain homogenates. Eur J Pharmacol. 1981 Apr 9;70(4):501-9. [Article]
- Kano M, Fukudo S, Tashiro A, Utsumi A, Tamura D, Itoh M, Iwata R, Tashiro M, Mochizuki H, Funaki Y, Kato M, Hongo M, Yanai K: Decreased histamine H1 receptor binding in the brain of depressed patients. Eur J Neurosci. 2004 Aug;20(3):803-10. [Article]
- Claro E, Arbones L, Garcia A, Picatoste F: Phosphoinositide hydrolysis mediated by histamine H1-receptors in rat brain cortex. Eur J Pharmacol. 1986 Apr 16;123(2):187-96. [Article]
- Richelson E, Nelson A: Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther. 1984 Jul;230(1):94-102. [Article]
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Stahl SM: Selective histamine H1 antagonism: novel hypnotic and pharmacologic actions challenge classical notions of antihistamines. CNS Spectr. 2008 Dec;13(12):1027-38. [Article]
- Singh H, Becker PM: Novel therapeutic usage of low-dose doxepin hydrochloride. Expert Opin Investig Drugs. 2007 Aug;16(8):1295-305. [Article]
- Figueiredo A, Ribeiro CA, Goncalo M, Almeida L, Poiares-Baptista A, Teixeira F: Mechanism of action of doxepin in the treatment of chronic urticaria. Fundam Clin Pharmacol. 1990;4(2):147-58. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- The H2 subclass of histamine receptors mediates gastric acid secretion. Also appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and differentiation. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and, through a separate G protein-dependent mechanism, the phosphoinositide/protein kinase (PKC) signaling pathway (By similarity)
- Specific Function
- G protein-coupled serotonin receptor activity
- Gene Name
- HRH2
- Uniprot ID
- P25021
- Uniprot Name
- Histamine H2 receptor
- Molecular Weight
- 40097.65 Da
References
- Beil W, Hannemann H, Sewing KF: Interaction of antidepressants and neuroleptics with histamine stimulated parietal cell adenylate cyclase and H+ secretion. Pharmacology. 1988;36(3):198-203. [Article]
- Figueiredo A, Ribeiro CA, Goncalo M, Almeida L, Poiares-Baptista A, Teixeira F: Mechanism of action of doxepin in the treatment of chronic urticaria. Fundam Clin Pharmacol. 1990;4(2):147-58. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- 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]
- Stahl SM: Selective histamine H1 antagonism: novel hypnotic and pharmacologic actions challenge classical notions of antihistamines. CNS Spectr. 2008 Dec;13(12):1027-38. [Article]
- Pagliaro L. and Pagliaro A. (1999). Psychologists' psychotropic drug reference. Taylor and Francis.
- 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
- 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]
- Stahl SM: Selective histamine H1 antagonism: novel hypnotic and pharmacologic actions challenge classical notions of antihistamines. CNS Spectr. 2008 Dec;13(12):1027-38. [Article]
- Pagliaro L. and Pagliaro A. (1999). Psychologists' psychotropic drug reference. Taylor and Francis.
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:1330647, PubMed:18703043, PubMed:19057895). 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). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors (PubMed:28129538). Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:28129538). Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores (PubMed:18703043, PubMed:28129538). 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
- 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
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Maj J, Gancarczyk L, Gorszczyk L, Rawlow A: Doxepin as a blocker of central serotonin receptors. Pharmakopsychiatr Neuropsychopharmakol. 1977 Dec;10(6):318-24. [Article]
- Stahl SM: Selective histamine H1 antagonism: novel hypnotic and pharmacologic actions challenge classical notions of antihistamines. CNS Spectr. 2008 Dec;13(12):1027-38. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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: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 down-stream effectors (PubMed:23519215, PubMed:28129538, 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). Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores (PubMed:18703043, PubMed:23519215, PubMed:28129538, PubMed:8078486, PubMed:8143856, PubMed:8882600). 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. Protects cardiomyocytes against apoptosis. Plays a role in the adaptation of pulmonary arteries to chronic hypoxia. Plays a role in vasoconstriction. Required for normal osteoblast function and proliferation, and for maintaining normal bone density. 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
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Maj J, Gancarczyk L, Gorszczyk L, Rawlow A: Doxepin as a blocker of central serotonin receptors. Pharmakopsychiatr Neuropsychopharmakol. 1977 Dec;10(6):318-24. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). 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). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis
- 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
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Maj J, Gancarczyk L, Gorszczyk L, Rawlow A: Doxepin as a blocker of central serotonin receptors. Pharmakopsychiatr Neuropsychopharmakol. 1977 Dec;10(6):318-24. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover
- Specific Function
- G protein-coupled acetylcholine receptor activity
- Gene Name
- CHRM1
- Uniprot ID
- P11229
- Uniprot Name
- Muscarinic acetylcholine receptor M1
- Molecular Weight
- 51420.375 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Stahl SM: Selective histamine H1 antagonism: novel hypnotic and pharmacologic actions challenge classical notions of antihistamines. CNS Spectr. 2008 Dec;13(12):1027-38. [Article]
- Ehlert FJ, Delen FM, Yun SH, Liem HA: The interaction of amitriptyline, doxepin, imipramine and their N-methyl quaternary ammonium derivatives with subtypes of muscarinic receptors in brain and heart. J Pharmacol Exp Ther. 1990 Apr;253(1):13-9. [Article]
- Figueiredo A, Ribeiro CA, Goncalo M, Almeida L, Poiares-Baptista A, Teixeira F: Mechanism of action of doxepin in the treatment of chronic urticaria. Fundam Clin Pharmacol. 1990;4(2):147-58. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol
- Specific Function
- Arrestin family protein binding
- Gene Name
- CHRM2
- Uniprot ID
- P08172
- Uniprot Name
- Muscarinic acetylcholine receptor M2
- Molecular Weight
- 51714.605 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Ehlert FJ, Delen FM, Yun SH, Liem HA: The interaction of amitriptyline, doxepin, imipramine and their N-methyl quaternary ammonium derivatives with subtypes of muscarinic receptors in brain and heart. J Pharmacol Exp Ther. 1990 Apr;253(1):13-9. [Article]
- Figueiredo A, Ribeiro CA, Goncalo M, Almeida L, Poiares-Baptista A, Teixeira F: Mechanism of action of doxepin in the treatment of chronic urticaria. Fundam Clin Pharmacol. 1990;4(2):147-58. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover
- Specific Function
- Acetylcholine binding
- Gene Name
- CHRM3
- Uniprot ID
- P20309
- Uniprot Name
- Muscarinic acetylcholine receptor M3
- Molecular Weight
- 66127.445 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Ehlert FJ, Delen FM, Yun SH, Liem HA: The interaction of amitriptyline, doxepin, imipramine and their N-methyl quaternary ammonium derivatives with subtypes of muscarinic receptors in brain and heart. J Pharmacol Exp Ther. 1990 Apr;253(1):13-9. [Article]
- Figueiredo A, Ribeiro CA, Goncalo M, Almeida L, Poiares-Baptista A, Teixeira F: Mechanism of action of doxepin in the treatment of chronic urticaria. Fundam Clin Pharmacol. 1990;4(2):147-58. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase
- Specific Function
- G protein-coupled acetylcholine receptor activity
- Gene Name
- CHRM4
- Uniprot ID
- P08173
- Uniprot Name
- Muscarinic acetylcholine receptor M4
- Molecular Weight
- 53048.65 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Ehlert FJ, Delen FM, Yun SH, Liem HA: The interaction of amitriptyline, doxepin, imipramine and their N-methyl quaternary ammonium derivatives with subtypes of muscarinic receptors in brain and heart. J Pharmacol Exp Ther. 1990 Apr;253(1):13-9. [Article]
- Figueiredo A, Ribeiro CA, Goncalo M, Almeida L, Poiares-Baptista A, Teixeira F: Mechanism of action of doxepin in the treatment of chronic urticaria. Fundam Clin Pharmacol. 1990;4(2):147-58. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover
- Specific Function
- G protein-coupled acetylcholine receptor activity
- Gene Name
- CHRM5
- Uniprot ID
- P08912
- Uniprot Name
- Muscarinic acetylcholine receptor M5
- Molecular Weight
- 60073.205 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Ehlert FJ, Delen FM, Yun SH, Liem HA: The interaction of amitriptyline, doxepin, imipramine and their N-methyl quaternary ammonium derivatives with subtypes of muscarinic receptors in brain and heart. J Pharmacol Exp Ther. 1990 Apr;253(1):13-9. [Article]
- Figueiredo A, Ribeiro CA, Goncalo M, Almeida L, Poiares-Baptista A, Teixeira F: Mechanism of action of doxepin in the treatment of chronic urticaria. Fundam Clin Pharmacol. 1990;4(2):147-58. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes
- Specific Function
- Alpha1-adrenergic receptor activity
- Gene Name
- ADRA1A
- Uniprot ID
- P35348
- Uniprot Name
- Alpha-1A adrenergic receptor
- Molecular Weight
- 51486.005 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Stahl SM: Selective histamine H1 antagonism: novel hypnotic and pharmacologic actions challenge classical notions of antihistamines. CNS Spectr. 2008 Dec;13(12):1027-38. [Article]
- Richelson E, Nelson A: Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther. 1984 Jul;230(1):94-102. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes
- Specific Function
- Alpha1-adrenergic receptor activity
- Gene Name
- ADRA1B
- Uniprot ID
- P35368
- Uniprot Name
- Alpha-1B adrenergic receptor
- Molecular Weight
- 56835.375 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Stahl SM: Selective histamine H1 antagonism: novel hypnotic and pharmacologic actions challenge classical notions of antihistamines. CNS Spectr. 2008 Dec;13(12):1027-38. [Article]
- Richelson E, Nelson A: Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther. 1984 Jul;230(1):94-102. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium
- Specific Function
- Alpha1-adrenergic receptor activity
- Gene Name
- ADRA1D
- Uniprot ID
- P25100
- Uniprot Name
- Alpha-1D adrenergic receptor
- Molecular Weight
- 60462.205 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Stahl SM: Selective histamine H1 antagonism: novel hypnotic and pharmacologic actions challenge classical notions of antihistamines. CNS Spectr. 2008 Dec;13(12):1027-38. [Article]
- Richelson E, Nelson A: Antagonism by antidepressants of neurotransmitter receptors of normal human brain in vitro. J Pharmacol Exp Ther. 1984 Jul;230(1):94-102. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli
- Specific Function
- G protein-coupled serotonin receptor activity
- Gene Name
- HTR1A
- Uniprot ID
- P08908
- Uniprot Name
- 5-hydroxytryptamine receptor 1A
- Molecular Weight
- 46106.335 Da
References
- Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [Article]
- Maj J, Gancarczyk L, Gorszczyk L, Rawlow A: Doxepin as a blocker of central serotonin receptors. Pharmakopsychiatr Neuropsychopharmakol. 1977 Dec;10(6):318-24. [Article]
- Stephen M. Stahl (2006). Essential Psychopharmacology: The Prescriber's Guide: Revised and Updated Edition. Cambridge University Press. [ISBN:9780521683500]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs (By similarity). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of TOR signaling (PubMed:23027611)
- Specific Function
- G protein-coupled serotonin receptor activity
- Gene Name
- HTR6
- Uniprot ID
- P50406
- Uniprot Name
- 5-hydroxytryptamine receptor 6
- Molecular Weight
- 46953.625 Da
References
- PDSP Ki Database [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Binder
- General Function
- The H4 subclass of histamine receptors could mediate the histamine signals in peripheral tissues. Displays a significant level of constitutive activity (spontaneous activity in the absence of agonist)
- Specific Function
- G protein-coupled acetylcholine receptor activity
- Gene Name
- HRH4
- Uniprot ID
- Q9H3N8
- Uniprot Name
- Histamine H4 receptor
- Molecular Weight
- 44495.375 Da
References
- PDSP Ki Database [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr) (PubMed:18559421, PubMed:26363003, PubMed:27916661)
- Specific Function
- C3hc4-type ring finger domain binding
- Gene Name
- KCNH2
- Uniprot ID
- Q12809
- Uniprot Name
- Potassium voltage-gated channel subfamily H member 2
- Molecular Weight
- 126653.52 Da
References
- Duncan RS, McPate MJ, Ridley JM, Gao Z, James AF, Leishman DJ, Leaney JL, Witchel HJ, Hancox JC: Inhibition of the HERG potassium channel by the tricyclic antidepressant doxepin. Biochem Pharmacol. 2007 Aug 1;74(3):425-37. Epub 2007 May 3. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
- Hartter S, Tybring G, Friedberg T, Weigmann H, Hiemke C: The N-demethylation of the doxepin isomers is mainly catalyzed by the polymorphic CYP2C19. Pharm Res. 2002 Jul;19(7):1034-7. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
- Szewczuk-Boguslawska M, Kiejna A, Beszlej JA, Orzechowska-Juzwenko K, Milejski P: Doxepin inhibits CYP2D6 activity in vivo. Pol J Pharmacol. 2004 Jul-Aug;56(4):491-4. [Article]
- Grasmader K, Verwohlt PL, Rietschel M, Dragicevic A, Muller M, Hiemke C, Freymann N, Zobel A, Maier W, Rao ML: Impact of polymorphisms of cytochrome-P450 isoenzymes 2C9, 2C19 and 2D6 on plasma concentrations and clinical effects of antidepressants in a naturalistic clinical setting. Eur J Clin Pharmacol. 2004 Jul;60(5):329-36. Epub 2004 May 28. [Article]
- Kirchheiner J, Meineke I, Muller G, Roots I, Brockmoller J: Contributions of CYP2D6, CYP2C9 and CYP2C19 to the biotransformation of E- and Z-doxepin in healthy volunteers. Pharmacogenetics. 2002 Oct;12(7):571-80. [Article]
- Haritos VS, Ghabrial H, Ahokas JT, Ching MS: Role of cytochrome P450 2D6 (CYP2D6) in the stereospecific metabolism of E- and Z-doxepin. Pharmacogenetics. 2000 Oct;10(7):591-603. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- 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
- Kirchheiner J, Meineke I, Muller G, Roots I, Brockmoller J: Contributions of CYP2D6, CYP2C9 and CYP2C19 to the biotransformation of E- and Z-doxepin in healthy volunteers. Pharmacogenetics. 2002 Oct;12(7):571-80. [Article]
- Hartter S, Tybring G, Friedberg T, Weigmann H, Hiemke C: The N-demethylation of the doxepin isomers is mainly catalyzed by the polymorphic CYP2C19. Pharm Res. 2002 Jul;19(7):1034-7. [Article]
- 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 and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). 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:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
- Specific Function
- (r)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Kirchheiner J, Meineke I, Muller G, Roots I, Brockmoller J: Contributions of CYP2D6, CYP2C9 and CYP2C19 to the biotransformation of E- and Z-doxepin in healthy volunteers. Pharmacogenetics. 2002 Oct;12(7):571-80. [Article]
- Hartter S, Tybring G, Friedberg T, Weigmann H, Hiemke C: The N-demethylation of the doxepin isomers is mainly catalyzed by the polymorphic CYP2C19. Pharm Res. 2002 Jul;19(7):1034-7. [Article]
- 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
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- 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
References
- Virtanen R, Iisalo E, Irjala K: Protein binding of doxepin and desmethyldoxepin. Acta Pharmacol Toxicol (Copenh). 1982 Aug;51(2):159-64. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Functions as a transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction
- Specific Function
- Not Available
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23539.43 Da
References
- Virtanen R, Iisalo E, Irjala K: Protein binding of doxepin and desmethyldoxepin. Acta Pharmacol Toxicol (Copenh). 1982 Aug;51(2):159-64. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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]
Drug created at June 13, 2005 13:24 / Updated at September 15, 2024 21:55