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Identification
- Summary
Aripiprazole lauroxil is an antipsychotic used to treat schizophrenia in adults.
- Brand Names
- Aristada
- Generic Name
- Aripiprazole lauroxil
- DrugBank Accession Number
- DB14185
- Background
Aripiprazole lauroxil is a long-acting injectable atypical antipsychotic drug used in the treatment of schizophrenia in adult patients. It is a prodrug of aripiprazole, which acts as a partial agonist at the D2 and 5-HT1A receptors, and as an antagonist at the 5-HT2A receptors 1.
Affecting about 1% of the adult population in the United States and approximately 26 million people worldwide, schizophrenia is a chronic neurological disorder that may result in impairments in cognition and executive functions 1. The quality of life in patients is greatly reduced due to negative health outcomes, and oftentimes the patients are faced with social stigma and discriminations. Schizophrenia is characterized by positive symptoms such as delusions, hallucinations, thought disorders, and catanoia, and negative symptoms that include social withdrawal, anhedonia, and flattening of emotional responses 7. D2 receptors have been the most common target for antipsychotic agents used in the treatment of schizophrenia: the positive symptoms are thought to arise from overactivity in the mesolimbic dopaminergic pathway activating D2 receptors, whereas negative symptoms may result from a decreased activity in the mesocortical dopaminergic pathway with D1 receptors predominating 7. In a randomized, double-blind clinical trial, treatment of aripiprazole lauroxil in adult patients with schizophrenia resulted in improvement of positive and negative symptoms scores at day 85 of treatment 1,3.
Aripiprazole lauroxil was initially approved by the FDA in October 2015 under the market name Aristada for the treatment of schizophrenia. It is administered via intramuscular injection, and requires the establishment of tolerability prior to dosing in treatment-naïve patients Label. On July 2nd, a different formulation of aripiprazole lauroxil marketed as Aristada Initio was FDA-approved for immediate initiation of Aristada at any dose. The patients may receive Aristada Initio in combination with a single 30 mg oral dose of aripiprazole to achieve appropriate levels of aripiprazole more rapidly. Long-acting injectable aripiprazole lauroxil displayed comparable efficacy and safety to aripiprazole 3, and reduced dosing frequency improves patient adherence.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Aripiprazole lauroxil (DB14185)
- Weight
- Average: 660.72
Monoisotopic: 659.3256625 - Chemical Formula
- C36H51Cl2N3O4
- Synonyms
- Aripiprazole lauroxil
- External IDs
- ALKS 9070
- ALKS 9072
- ALKS-9070
- ALKS-9072
- RDC-3317
- RDC3317
Pharmacology
- Indication
Aripiprazole lauroxil is indicated for the treatment of schizophrenia and related psychotic disorders.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to manage Schizophrenia Regimen in combination with: Aripiprazole (DB01238) •••••••••••• ••••• •••••••••• •••••••••• ••••••••••• •••••••• ••••••• Management of Schizophrenia •••••••••••• ••••• •••••••••• •••••••••• ••••••••••• •••••••• ••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Aripiprazole, which is a major pharmacological metabolite of aripiprazole lauroxil, serves to improve the positive and negative symptoms of schizophrenia by modulating dopaminergic signalling pathways. Aripiprazole lauroxil is reported to have minimal effects on sexual function or prolactin levels 7.
- Mechanism of action
The pharmacological activity of aripiprazole lauroxil is thought to be mainly mediated by its metabolite aripiprazole, and to a lesser extent, dehydro-aripiprazole. Aripiprazole functions as a partial agonist at the dopamine D2 and the serotonin 5-HT1A receptors, and as an antagonist at the serotonin 5-HT2A receptor Label. The desired outcome of antipsuchotic agents in schizophrenia is to inhibit dopaminergic transmission in the limbic system and enhance dopaminergic transmission in the prefrontal cortex. As a partial agonist at D2 receptors in the mesolimbic dopaminergic pathway, aripiprazole acts as a functional antagonist in the mesolimbic dopamine pathway and reduces the extent of dopaminergic pathway activity. This results in reduced positive symptoms in schizophrenia and extrapyramidal motor side effects 6. In contrast, aripiprazole is thought to act as a functional agonist in the mesocortical pathway, where reduced dopamine activity is seen in association with negative symptoms and cognitive impairment 6. Antagonism at 5-HT2A receptors by aripiprazole alleviates the negative symptoms and cognitive impairment of schizophrenia 7. 5-HT2A receptors are Gi/Go-coupled that upon activation, produce neuronal inhibition via decreased neuronal excitability and decreased transmitter release at the nerve terminals. In the nigrostriatal pathway, 5-HT2A regulates the release of dopamine. Through antagonism of 5-HT2A receptors, aripiprazole disinhibits the release of dopamine in the striatum and enhance the levels of the transmitters at the nerve terminals 7. The combined effects of D2 and 5-HT2A antagonism are thought to counteract the increased dopamine function causing increased extrapyramidal side effects 7. Blocking 5-HT2A receptors may also lead to the modulation of glutamate release in the mesocortical circuit, which is a transmitter that plays a role in schizophrenia 6. 5-HT1A receptors are autoreceptors that inhibit 5-HT release upon activation. Aripiprazole is a partial agonist at theses receptors and reduces 5-HT release; this results in potentiated dopamine release in the striatum and prefrontal cortex 7. It is reported that therapeutic doses of aripiprazole occupies up to 90% of brain D2 receptors in a dose-dependent manner 4.
Apripiprazole targets different receptors that lead to drug-related adverse reactions; for example, the antagonist activity at the alpha-1 adrenergic receptors results in orthostatic hypotension 1. Aripiprazole's antagonism of histamine H1 receptors may explain the somnolence observed with this drug 1.
- Absorption
Following a single extended-release intramuscular injection of aripiprazole lauroxil, aripiprazole can be detected in the systemic circulation from 5 to 6 days and is continued to be released for an additional 36 days. The concentrations of aripiprazole increases with consecutive doses of aripiprazole lauroxil and the steady state is reached following the fourth monthly injection Label. The systemic exposure to aripiprazole was similar when comparing deltoid and gluteal intramuscular injections Label.
- Volume of distribution
Based on population pharmacokinetic analysis, the apparent volume of distribution of aripiprazole following intramuscular injection of aripiprazole lauroxil was 268 L, indicating extensive extravascular distribution following absorption Label. Health human volunteer study indicates that aripiprazole crosses the blood-brain barrier Label.
- Protein binding
Serum protein binding of aripiprazole and its major metabolite is >99% at therapeutic concentrations, where they are primarily bound to albumin Label.
- Metabolism
Aripiprazole lauroxil is hydrolyzed to form N-hydroxymethyl-aripiprazole via esterases. N-hydroxymethyl-aripiprazole undergoes a rapid, nonenzymatic spontaneous cleavage, or water-mediated hydrolysis, to form aripiprazole, which mainly contributes to the pharmacological actions of aripiprazole lauroxil. Aripiprazole is further metabolized by hepatic CYP3A4 and CYP2D6 to form dehydro-aripiprazole, which retains some pharmacological activity. Dehydro-aripiprazole displays affinities for D2 receptors similar to aripiprazole and represents 30-40% of the aripiprazole exposure in plasma Label. Cytochrome P450 2D6 is subject to genetic polymorphism, which results in pharmacokinetic differences among CYP2D6 metabolizer phenotypes and dosage adjustments accordingly 1.
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- Route of elimination
Based on the pharmacokinetic study for aripiprazole, less than 1% of unchanged aripiprazole was excreted in the urine and approximately 18% of the oral dose was recovered unchanged in the feces 9.
- Half-life
The mean aripiprazole terminal elimination half-life ranged from 29.2 days to 34.9 days after every 4-week injection of aripiprazole lauroxil 441, 662 and 882 mg Label.
- Clearance
In rats, the clearance for aripiprazole lauroxil was 0.32 ± 0.11 L/h/kg following injection of aripiprazole lauroxil molar equivalent to 5 mg aripiprazole/kg 5.
- Adverse Effects
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LD50 in rat following intramuscular injection was >60 mg aripiprazole equivalents MSDS. Oral LD50 of aripiprazole in female rat, male rat, and monkey were 705 mg/kg, 965 mg/kg, and >2000 mg/kg, respectively MSDS. Most common adverse reaction of aripiprazole was akathisia. A case of drug overdosage occurred followinga acute ingestion of 1260 mg aripiprazole, which is approximately 42 times the maximum recommended daily dose. Overdose was associated with vomiting, somnolence, and tremor Label. Other clinically important signs and symptoms observed in one or more patients with aripiprazole overdoses (alone or with other substances) include acidosis, aggression, aspartate aminotransferase increased, atrial fibrillation, bradycardia, coma, confusional state, convulsion, blood creatine phosphokinase increased, depressed level of consciousness, hypertension, hypokalemia, hypotension, lethargy, loss of consciousness, QRS complex prolonged, QT prolonged, pneumonia aspiration, respiratory arrest, status epilepticus, and tachycardia Label.
Aripiprazole is an antipsychotic drug that may develop Neuroleptic Malignant Syndrome (NMS), which is manifested with hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability. In case of NMS, aripiprazole should be discontinued immediately, and intensive symptomatic treatment and medical monitoring should be initiated Label.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
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 1,2-Benzodiazepine is combined with Aripiprazole lauroxil. Abaloparatide Aripiprazole lauroxil may increase the hypotensive activities of Abaloparatide. Abametapir The serum concentration of Aripiprazole lauroxil can be increased when it is combined with Abametapir. Abatacept The metabolism of Aripiprazole lauroxil can be increased when combined with Abatacept. Abiraterone The metabolism of Aripiprazole lauroxil can be decreased when combined with Abiraterone. - Food Interactions
- No interactions found.
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.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Aristada Injection, suspension, extended release 662 mg/2.4mL Intramuscular Alkermes, Inc. 2015-10-05 Not applicable US 
Aristada Injection, suspension, extended release 441 mg/1.6mL Intramuscular Alkermes, Inc. 2015-10-05 Not applicable US Aristada Injection, suspension, extended release 1064 mg/3.9mL Intramuscular Alkermes, Inc. 2017-06-05 Not applicable US Aristada Injection, suspension, extended release 882 mg/3.2mL Intramuscular Alkermes, Inc. 2015-10-05 Not applicable US Aristada Initio Injection, suspension, extended release 675 mg/2.4mL Intramuscular Alkermes, Inc. 2018-06-29 Not applicable US
Categories
- Drug Categories
- Adrenergic alpha-1 Receptor Antagonists
- Adrenergic alpha-Antagonists
- Adrenergic Antagonists
- Agents that produce hypertension
- Antidepressive Agents
- Antipsychotic Agents
- Antipsychotic Agents (Second Generation [Atypical])
- Aripiprazole and prodrugs
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 CYP3A7 Substrates
- Cytochrome P-450 Substrates
- Heterocyclic Compounds, Fused-Ring
- Histamine Antagonists
- Histamine H1 Antagonists
- Neurotoxic agents
- Piperazines
- Potential QTc-Prolonging Agents
- Psychotropic Drugs
- QTc Prolonging Agents
- Quinolines
- Quinolones
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin 5-HT2 Receptor Antagonists
- Serotonin 5-HT2A Receptor Antagonists
- Serotonin Agents
- Serotonin Receptor Antagonists
- Tranquilizing Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylpiperazines. These are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazinanes
- Sub Class
- Piperazines
- Direct Parent
- Phenylpiperazines
- Alternative Parents
- N-arylpiperazines / Hydroquinolones / Hydroquinolines / Aniline and substituted anilines / Dialkylarylamines / Dichlorobenzenes / N-alkylpiperazines / Fatty acid esters / Alkyl aryl ethers / Aryl chlorides show 12 more
- Substituents
- 1,2-dichlorobenzene / Alkyl aryl ether / Amine / Amino acid or derivatives / Aniline or substituted anilines / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid show 32 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- B786J7A343
- CAS number
- 1259305-29-7
- InChI Key
- DDINXHAORAAYAD-UHFFFAOYSA-N
- InChI
- InChI=1S/C36H51Cl2N3O4/c1-2-3-4-5-6-7-8-9-10-16-35(43)45-28-41-33-27-30(19-17-29(33)18-20-34(41)42)44-26-12-11-21-39-22-24-40(25-23-39)32-15-13-14-31(37)36(32)38/h13-15,17,19,27H,2-12,16,18,20-26,28H2,1H3
- IUPAC Name
- (7-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butoxy}-2-oxo-1,2,3,4-tetrahydroquinolin-1-yl)methyl dodecanoate
- SMILES
- CCCCCCCCCCCC(=O)OCN1C(=O)CCC2=CC=C(OCCCCN3CCN(CC3)C3=C(Cl)C(Cl)=CC=C3)C=C12
References
- General References
- Cruz MP: Aripiprazole Lauroxil (Aristada): An Extended-Release, Long-Acting Injection For the Treatment of Schizophrenia. P T. 2016 Sep;41(9):556-9. [Article]
- Raedler LA: Aripiprazole Lauroxil (Aristada): Long-Acting Atypical Antipsychotic Injection Approved for the Treatment of Patients with Schizophrenia. Am Health Drug Benefits. 2016 Mar;9(Spec Feature):40-3. [Article]
- Potkin SG, Risinger R, Du Y, Zummo J, Bose A, Silverman B, Stankovic S, Ehrich E: Efficacy and safety of aripiprazole lauroxil in schizophrenic patients presenting with severe psychotic symptoms during an acute exacerbation. Schizophr Res. 2017 Dec;190:115-120. doi: 10.1016/j.schres.2017.03.003. Epub 2017 Mar 23. [Article]
- Seeman P: Dopamine D2 receptors as treatment targets in schizophrenia. Clin Schizophr Relat Psychoses. 2010 Apr;4(1):56-73. doi: 10.3371/CSRP.4.1.5. [Article]
- Rohde M, M Rk N, Hakansson AE, Jensen KG, Pedersen H, Dige T, J Rgensen EB, Holm R: Biological conversion of aripiprazole lauroxil - An N-acyloxymethyl aripiprazole prodrug. Results Pharma Sci. 2014 May 2;4:19-25. doi: 10.1016/j.rinphs.2014.04.002. eCollection 2014. [Article]
- Lieberman JA: Dopamine partial agonists: a new class of antipsychotic. CNS Drugs. 2004;18(4):251-67. [Article]
- 45. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 553-557). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
- FDA Approved Drug Products: ARISTADA (aripiprazole lauroxil) injectable [Link]
- ABILIFY (aripiprazole)Tablets FDA Label [File]
- External Links
- KEGG Drug
- D10364
- ChemSpider
- 28651973
- ChEBI
- 90930
- ChEMBL
- CHEMBL2219425
- ZINC
- ZINC000095564895
- PharmGKB
- PA166161216
- Wikipedia
- Aripiprazole_lauroxil
- FDA label
- Download (948 KB)
- MSDS
- Download (269 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 data4 Completed Treatment Schizophrenia 1 somestatus stop reason just information to hide 4 Recruiting Treatment Schizophrenia 1 somestatus stop reason just information to hide 4 Terminated Treatment Schizoaffective Disorder, Depressive Type / Schizophrenia / Schizophreniform Disorders 1 somestatus stop reason just information to hide 4 Withdrawn Treatment Major Depressive Disorder (MDD) 1 somestatus stop reason just information to hide 3 Completed Treatment Schizophrenia 4 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, suspension, extended release Intramuscular 1064 mg/3.9mL Injection, suspension, extended release Intramuscular 441 mg/1.6mL Injection, suspension, extended release Intramuscular 662 mg/2.4mL Injection, suspension, extended release Intramuscular 882 mg/3.2mL Injection, suspension, extended release Intramuscular 675 mg/2.4mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9193685 No 2015-11-24 2033-10-24 US US8796276 No 2014-08-05 2030-06-24 US US9034867 No 2015-05-19 2032-11-07 US US8431576 No 2013-04-30 2030-10-26 US US9526726 No 2016-12-27 2035-03-19 US US9452131 No 2016-09-27 2035-03-19 US US10016415 No 2018-07-10 2035-09-08 US US10112903 No 2018-10-30 2030-06-24 US US10226458 No 2019-03-12 2032-11-07 US US10238651 No 2019-03-26 2035-03-19 US US10688091 No 2020-06-23 2035-08-17 US US10849894 No 2020-12-01 2035-08-17 US US10813928 No 2020-10-27 2035-03-19 US US11097006 No 2021-08-24 2033-10-24 US US11154552 No 2021-10-26 2035-08-17 US US11273158 No 2019-04-06 2039-04-06 US US11406632 No 2015-03-19 2035-03-19 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 81-83 MSDS water solubility <0.01 mg/mL MSDS logP 5.3 MSDS - Predicted Properties
Property Value Source Water Solubility 0.000237 mg/mL ALOGPS logP 7.91 ALOGPS logP 9.33 Chemaxon logS -6.4 ALOGPS pKa (Strongest Basic) 7.46 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 62.32 Å2 Chemaxon Rotatable Bond Count 20 Chemaxon Refractivity 183.74 m3·mol-1 Chemaxon Polarizability 76.95 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 251.56047 predictedDeepCCS 1.0 (2019) [M+H]+ 253.95604 predictedDeepCCS 1.0 (2019) [M+Na]+ 259.8686 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Partial agonist
- General Function
- Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (PubMed:21645528). Positively regulates postnatal regression of retinal hyaloid vessels via suppression of VEGFR2/KDR activity, downstream of OPN5 (By similarity)
- Specific Function
- dopamine binding
- Gene Name
- DRD2
- Uniprot ID
- P14416
- Uniprot Name
- D(2) dopamine receptor
- Molecular Weight
- 50618.91 Da
References
- Hirose T, Kikuchi T: Aripiprazole, a novel antipsychotic agent: dopamine D2 receptor partial agonist. J Med Invest. 2005 Nov;52 Suppl:284-90. [Article]
- Inoue A, Miki S, Seto M, Kikuchi T, Morita S, Ueda H, Misu Y, Nakata Y: Aripiprazole, a novel antipsychotic drug, inhibits quinpirole-evoked GTPase activity but does not up-regulate dopamine D2 receptor following repeated treatment in the rat striatum. Eur J Pharmacol. 1997 Feb 19;321(1):105-11. [Article]
- Wood MD, Scott C, Clarke K, Westaway J, Davies CH, Reavill C, Hill M, Rourke C, Newson M, Jones DN, Forbes IT, Gribble A: Aripiprazole and its human metabolite are partial agonists at the human dopamine D2 receptor, but the rodent metabolite displays antagonist properties. Eur J Pharmacol. 2006 Sep 28;546(1-3):88-94. Epub 2006 Jul 21. [Article]
- Kim E, Yu KS, Cho JY, Shin YW, Yoo SY, Kim YY, Jang IJ, Shin SG, Kwon JS: Effects of DRD2 and CYP2D6 genotypes on delta EEG power response to aripiprazole in healthy male volunteers: a preliminary study. Hum Psychopharmacol. 2006 Dec;21(8):519-28. [Article]
- Wood M, Reavill C: Aripiprazole acts as a selective dopamine D2 receptor partial agonist. Expert Opin Investig Drugs. 2007 Jun;16(6):771-5. [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
- Partial agonist
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:22957663, PubMed:3138543, PubMed:33762731, PubMed:37935376, PubMed:37935377, PubMed:8138923, PubMed:8393041). Also functions as a receptor for various drugs and psychoactive substances (PubMed:22957663, PubMed:3138543, PubMed:33762731, PubMed:38552625, PubMed:8138923, PubMed:8393041). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:22957663, PubMed:3138543, PubMed:33762731, PubMed:8138923, PubMed:8393041). HTR1A is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission: signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores (PubMed:33762731, PubMed:35610220). Beta-arrestin family members regulate signaling by mediating both receptor desensitization and resensitization processes (PubMed:18476671, PubMed:20363322, PubMed:20945968). Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism (PubMed:18476671, PubMed:20363322, PubMed:20945968). Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior (PubMed:18476671, PubMed:20363322, PubMed:20945968). Plays a role in the response to anxiogenic stimuli (PubMed:18476671, PubMed:20363322, PubMed:20945968)
- 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
- Jordan S, Koprivica V, Chen R, Tottori K, Kikuchi T, Altar CA: The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor. Eur J Pharmacol. 2002 Apr 26;441(3):137-40. [Article]
- Marona-Lewicka D, Nichols DE: Aripiprazole (OPC-14597) fully substitutes for the 5-HT1A receptor agonist LY293284 in the drug discrimination assay in rats. Psychopharmacology (Berl). 2004 Apr;172(4):415-21. Epub 2003 Nov 28. [Article]
- Jordan S, Koprivica V, Dunn R, Tottori K, Kikuchi T, Altar CA: In vivo effects of aripiprazole on cortical and striatal dopaminergic and serotonergic function. Eur J Pharmacol. 2004 Jan 1;483(1):45-53. [Article]
- Swainston Harrison T, Perry CM: Aripiprazole: a review of its use in schizophrenia and schizoaffective disorder. Drugs. 2004;64(15):1715-36. [Article]
- Cosi C, Waget A, Rollet K, Tesori V, Newman-Tancredi A: Clozapine, ziprasidone and aripiprazole but not haloperidol protect against kainic acid-induced lesion of the striatum in mice, in vivo: role of 5-HT1A receptor activation. Brain Res. 2005 May 10;1043(1-2):32-41. [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
- Meltzer HY, Li Z, Kaneda Y, Ichikawa J: Serotonin receptors: their key role in drugs to treat schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Oct;27(7):1159-72. [Article]
- Stark AD, Jordan S, Allers KA, Bertekap RL, Chen R, Mistry Kannan T, Molski TF, Yocca FD, Sharp T, Kikuchi T, Burris KD: Interaction of the novel antipsychotic aripiprazole with 5-HT1A and 5-HT 2A receptors: functional receptor-binding and in vivo electrophysiological studies. Psychopharmacology (Berl). 2007 Feb;190(3):373-82. Epub 2006 Nov 25. [Article]
- Bortolozzi A, Diaz-Mataix L, Toth M, Celada P, Artigas F: In vivo actions of aripiprazole on serotonergic and dopaminergic systems in rodent brain. Psychopharmacology (Berl). 2007 Apr;191(3):745-58. Epub 2007 Jan 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:10452531, PubMed:1315531, PubMed:1328844, PubMed:1348246, PubMed:1351684, PubMed:1559993, PubMed:1565658, PubMed:1610347, PubMed:23519210, PubMed:23519215, PubMed:29925951, PubMed:8218242). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances, such as lysergic acid diethylamide (LSD) (PubMed:23519210, PubMed:23519215, PubMed:29925951). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:10452531, PubMed:1315531, PubMed:1328844, PubMed:1348246, PubMed:1351684, PubMed:1559993, PubMed:1565658, PubMed:1610347, PubMed:23519210, PubMed:23519215, PubMed:29925951, PubMed:8218242). HTR1B is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission by inhibiting adenylate cyclase activity (PubMed:29925951, PubMed:35610220). Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways (PubMed:29925951). Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior (PubMed:18476671, PubMed:20945968). Besides, plays a role in vasoconstriction of cerebral arteries (PubMed:15853772)
- Specific Function
- G protein-coupled serotonin receptor activity
- Gene Name
- HTR1B
- Uniprot ID
- P28222
- Uniprot Name
- 5-hydroxytryptamine receptor 1B
- Molecular Weight
- 43567.535 Da
References
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:10452531, PubMed:1565658, PubMed:1652050, PubMed:33762731). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive substances (PubMed:10452531, PubMed:1565658, PubMed:1652050, PubMed:33762731). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:10452531, PubMed:1565658, PubMed:1652050, PubMed:33762731). HTR1D is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission by inhibiting adenylate cyclase activity (PubMed:33762731). Regulates the release of 5-hydroxytryptamine in the brain, and thereby affects neural activity (PubMed:18476671, PubMed:20945968). May also play a role in regulating the release of other neurotransmitters (PubMed:18476671, PubMed:20945968). May play a role in vasoconstriction (PubMed:18476671, PubMed:20945968)
- Specific Function
- G protein-coupled serotonin receptor activity
- Gene Name
- HTR1D
- Uniprot ID
- P28221
- Uniprot Name
- 5-hydroxytryptamine receptor 1D
- Molecular Weight
- 41906.38 Da
References
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin) (PubMed:14744596, PubMed:1513320, PubMed:1608964, PubMed:1733778, PubMed:21422162, PubMed:33762731). Also functions as a receptor for various alkaloids and psychoactive substances (PubMed:14744596, PubMed:1513320, PubMed:1608964, PubMed:1733778, PubMed:21422162, PubMed:33762731). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:14744596, PubMed:1513320, PubMed:1608964, PubMed:1733778, PubMed:21422162, PubMed:33762731). HTR1E is coupled to G(i)/G(o) G alpha proteins and mediates inhibitory neurotransmission by inhibiting adenylate cyclase activity (PubMed:33762731, PubMed:35610220)
- Specific Function
- G protein-coupled receptor activity
- Gene Name
- HTR1E
- Uniprot ID
- P28566
- Uniprot Name
- 5-hydroxytryptamine receptor 1E
- Molecular Weight
- 41681.57 Da
References
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase
- Specific Function
- arrestin family protein binding
- Gene Name
- DRD1
- Uniprot ID
- P21728
- Uniprot Name
- D(1A) dopamine receptor
- Molecular Weight
- 49292.765 Da
References
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase
- Specific Function
- dopamine binding
- Gene Name
- DRD5
- Uniprot ID
- P21918
- Uniprot Name
- D(1B) dopamine receptor
- Molecular Weight
- 52950.5 Da
References
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation
- Specific Function
- dopamine neurotransmitter receptor activity, coupled via Gi/Go
- Gene Name
- DRD3
- Uniprot ID
- P35462
- Uniprot Name
- D(3) dopamine receptor
- Molecular Weight
- 44194.315 Da
References
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Curator comments
- Aripiprazole displays moderate affinity toward the receptor with a moderate affinity and Ki of 44 nM.
- General Function
- Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Activated by dopamine, but also by epinephrine and norepinephrine, and by numerous synthetic agonists and drugs (PubMed:16423344, PubMed:27659709, PubMed:29051383, PubMed:9003072). Agonist binding triggers signaling via G proteins that inhibit adenylyl cyclase (PubMed:16423344, PubMed:27659709, PubMed:29051383, PubMed:7512953, PubMed:7643093). Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity)
- Specific Function
- dopamine binding
- Gene Name
- DRD4
- Uniprot ID
- P21917
- Uniprot Name
- D(4) dopamine receptor
- Molecular Weight
- 43900.84 Da
References
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Curator comments
- Aripiprazole displays moderate affinity toward the receptor with a moderate affinity and Ki of 15 nM.
- 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
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons
- Specific Function
- excitatory extracellular ligand-gated monoatomic ion channel activity
- Gene Name
- HTR3A
- Uniprot ID
- P46098
- Uniprot Name
- 5-hydroxytryptamine receptor 3A
- Molecular Weight
- 55279.835 Da
References
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone and a mitogen (PubMed:35714614, PubMed:36989299, PubMed:37327704, PubMed:8522988). Also has a high affinity for tricyclic psychotropic drugs (By similarity). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:35714614). HTR6 is coupled to G(s) G alpha proteins and mediates activation of adenylate cyclase activity (PubMed:35714614, PubMed:37327704). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of mTOR 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
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Curator comments
- Aripiprazole displays moderate affinity toward the receptor with a moderate affinity and Ki of 39 nM.
- General Function
- G-protein coupled receptor for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone and a mitogen (PubMed:35714614, PubMed:8226867). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:35714614, PubMed:8226867). HTR7 is coupled to G(s) G alpha proteins and mediates activation of adenylate cyclase activity (PubMed:35714614)
- Specific Function
- G protein-coupled serotonin receptor activity
- Gene Name
- HTR7
- Uniprot ID
- P34969
- Uniprot Name
- 5-hydroxytryptamine receptor 7
- Molecular Weight
- 53554.43 Da
References
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Antagonist
- Curator comments
- Aripiprazole displays moderate affinity toward the receptor with a moderate affinity and Ki of 61 nM.
- General Function
- G-protein-coupled receptor for histamine, a biogenic amine that functions as an immune modulator and a neurotransmitter (PubMed:33828102, PubMed:8280179). Through the H1 receptor, histamine mediates the contraction of smooth muscles and increases capillary permeability due to contraction of terminal venules. Also mediates neurotransmission in the central nervous system and thereby regulates circadian rhythms, emotional and locomotor activities as well as cognitive functions (By similarity)
- 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
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Antagonist
- Curator comments
- Aripiprazole displays moderate affinity toward the receptor with a moderate affinity and Ki of 57 nM.
- 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
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Antagonist
- Curator comments
- Aripiprazole displays moderate affinity toward the receptor with a moderate affinity and Ki of 57 nM.
- 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
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- General Function
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol
- Specific Function
- alpha-1B adrenergic receptor binding
- Gene Name
- ADRA2A
- Uniprot ID
- P08913
- Uniprot Name
- Alpha-2A adrenergic receptor
- Molecular Weight
- 50646.17 Da
References
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- General Function
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol
- Specific Function
- alpha2-adrenergic receptor activity
- Gene Name
- ADRA2B
- Uniprot ID
- P18089
- Uniprot Name
- Alpha-2B adrenergic receptor
- Molecular Weight
- 49953.145 Da
References
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- General Function
- Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins
- Specific Function
- alpha-2A adrenergic receptor binding
- Gene Name
- ADRA2C
- Uniprot ID
- P18825
- Uniprot Name
- Alpha-2C adrenergic receptor
- Molecular Weight
- 49521.585 Da
References
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Curator comments
- According to the FDA label, aripiprazole has no appreciable affinity for cholinergic muscarinic receptors (IC50>1000 nM).
- 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
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Curator comments
- According to the FDA label, aripiprazole has no appreciable affinity for cholinergic muscarinic receptors (IC50>1000 nM).
- 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
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Curator comments
- IC50 is >1000 nM.
- 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
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Curator comments
- According to the FDA label, aripiprazole has no appreciable affinity for cholinergic muscarinic receptors (IC50>1000 nM).
- 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
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Curator comments
- According to the FDA label, aripiprazole has no appreciable affinity for cholinergic muscarinic receptors (IC50>1000 nM).
- 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
- Nasrallah HA: Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry. 2008 Jan;13(1):27-35. Epub 2007 Sep 11. [Article]
Enzymes
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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 steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). 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:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion 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 all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
- Specific Function
- aromatase activity
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins during embryogenesis (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). 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:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone, DHEA), a precursor in the biosynthesis of androgen and estrogen steroid hormones (PubMed:17178770, PubMed:9555064). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1), particularly D-ring hydroxylated estrone at the C16-alpha position (PubMed:12865317, PubMed:14559847). Mainly hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in atRA clearance during fetal development (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics including anticonvulsants (PubMed:9555064)
- Specific Function
- all-trans retinoic acid 18-hydroxylase activity
- Gene Name
- CYP3A7
- Uniprot ID
- P24462
- Uniprot Name
- Cytochrome P450 3A7
- Molecular Weight
- 57469.95 Da
References
- Flockhart Table of Drug Interactions [Link]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
Drug created at July 03, 2018 17:32 / Updated at September 05, 2021 20:19