Identification

Name
Aripiprazole lauroxil
Accession Number
DB14185  (DBSALT001351)
Type
Small Molecule
Groups
Approved, Investigational
Description

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.

Structure
Thumb
Synonyms
Not Available
External IDs
ALKS 9070 / ALKS 9072 / ALKS-9070 / ALKS-9072 / RDC-3317 / RDC3317
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AristadaInjection, suspension, extended release882 mg/3.2mLIntramuscularAlkermes, Inc.2015-10-05Not applicableUs
AristadaInjection, suspension, extended release662 mg/2.4mLIntramuscularAlkermes, Inc.2015-10-05Not applicableUs
AristadaInjection, suspension, extended release1064 mg/3.9mLIntramuscularAlkermes, Inc.2017-06-05Not applicableUs
AristadaInjection, suspension, extended release441 mg/1.6mLIntramuscularAlkermes, Inc.2015-10-05Not applicableUs
Aristada InitioInjection, suspension, extended release675 mg/2.4mLIntramuscularAlkermes, Inc.2018-06-29Not applicableUs
Categories
UNII
B786J7A343
CAS number
1259305-29-7
Weight
Average: 660.72
Monoisotopic: 659.3256625
Chemical Formula
C36H51Cl2N3O4
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

Pharmacology

Indication

Aripiprazole lauroxil is indicated for the treatment of schizophrenia and related psychotic disorders.

Associated Conditions
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].

TargetActionsOrganism
AD(2) dopamine receptor
partial agonist
Human
A5-hydroxytryptamine receptor 1A
partial agonist
Human
A5-hydroxytryptamine receptor 2A
antagonist
Human
U5-hydroxytryptamine receptor 1BNot AvailableHuman
U5-hydroxytryptamine receptor 1DNot AvailableHuman
U5-hydroxytryptamine receptor 1ENot AvailableHuman
UD(1A) dopamine receptorNot AvailableHuman
UD(1B) dopamine receptorNot AvailableHuman
UD(3) dopamine receptorNot AvailableHuman
UD(4) dopamine receptorNot AvailableHuman
U5-hydroxytryptamine receptor 2CNot AvailableHuman
U5-hydroxytryptamine receptor 3ANot AvailableHuman
U5-hydroxytryptamine receptor 6Not AvailableHuman
U5-hydroxytryptamine receptor 7Not AvailableHuman
NHistamine H1 receptor
antagonist
Human
NAlpha-1A adrenergic receptor
antagonist
Human
NAlpha-1B adrenergic receptor
antagonist
Human
NAlpha-2A adrenergic receptorNot AvailableHuman
NAlpha-2B adrenergic receptorNot AvailableHuman
NAlpha-2C adrenergic receptorNot AvailableHuman
NMuscarinic acetylcholine receptor M1Not AvailableHuman
NMuscarinic acetylcholine receptor M2Not AvailableHuman
NMuscarinic acetylcholine receptor M3Not AvailableHuman
NMuscarinic acetylcholine receptor M4Not AvailableHuman
NMuscarinic acetylcholine receptor M5Not AvailableHuman
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].

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 [8].

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].

Toxicity

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].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of adverse effects can be increased when Aripiprazole lauroxil is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of adverse effects can be increased when Aripiprazole lauroxil is combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when 2,5-Dimethoxy-4-ethylamphetamine is combined with Aripiprazole lauroxil.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of serotonin syndrome can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Aripiprazole lauroxil.
3,4-MethylenedioxyamphetamineThe risk or severity of serotonin syndrome can be increased when 3,4-Methylenedioxyamphetamine is combined with Aripiprazole lauroxil.
3,5-diiodothyropropionic acidThe metabolism of Aripiprazole lauroxil can be decreased when combined with 3,5-diiodothyropropionic acid.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of serotonin syndrome can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Aripiprazole lauroxil.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Aripiprazole lauroxil.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Methoxyamphetamine is combined with Aripiprazole lauroxil.
5-androstenedioneThe metabolism of Aripiprazole lauroxil can be decreased when combined with 5-androstenedione.
Food Interactions
Not Available

References

General References
  1. Cruz MP: Aripiprazole Lauroxil (Aristada): An Extended-Release, Long-Acting Injection For the Treatment of Schizophrenia. P T. 2016 Sep;41(9):556-9. [PubMed:27630522]
  2. 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. [PubMed:27668044]
  3. 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. [PubMed:28342578]
  4. 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. [PubMed:20643630]
  5. 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. [PubMed:25756003]
  6. Lieberman JA: Dopamine partial agonists: a new class of antipsychotic. CNS Drugs. 2004;18(4):251-67. [PubMed:15015905]
  7. 45. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 553-557). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
  8. ABILIFY (aripiprazole)Tablets FDA Label [File]
External Links
KEGG Drug
D10364
ChemSpider
28651973
ChEBI
90930
ChEMBL
CHEMBL2219425
PharmGKB
PA166161216
Wikipedia
Aripiprazole_lauroxil
FDA label
Download (948 KB)
MSDS
Download (269 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentSchizophrenic Disorders1
3CompletedTreatmentSchizophrenic Disorders3

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, suspension, extended releaseIntramuscular1064 mg/3.9mL
Injection, suspension, extended releaseIntramuscular441 mg/1.6mL
Injection, suspension, extended releaseIntramuscular662 mg/2.4mL
Injection, suspension, extended releaseIntramuscular882 mg/3.2mL
Injection, suspension, extended releaseIntramuscular675 mg/2.4mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US9193685No2015-11-242033-10-24Us
US8796276No2014-08-052030-06-24Us
US9034867No2015-05-192032-11-07Us
US8431576No2013-04-302030-10-26Us
US9526726No2016-12-272035-03-19Us
US9452131No2016-09-272035-03-19Us
US10016415No2015-09-082035-09-08Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)81-83MSDS
water solubility<0.01 mg/mLMSDS
logP5.3MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.000237 mg/mLALOGPS
logP7.91ALOGPS
logP9.33ChemAxon
logS-6.4ALOGPS
pKa (Strongest Basic)7.46ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area62.32 Å2ChemAxon
Rotatable Bond Count20ChemAxon
Refractivity183.74 m3·mol-1ChemAxon
Polarizability76.95 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

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
Phenylpiperazine / N-arylpiperazine / Tetrahydroquinolone / Quinolone / Tetrahydroquinoline / Tertiary aliphatic/aromatic amine / 1,2-dichlorobenzene / Aniline or substituted anilines / Dialkylarylamine / Alkyl aryl ether
show 32 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Partial agonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Hirose T, Kikuchi T: Aripiprazole, a novel antipsychotic agent: dopamine D2 receptor partial agonist. J Med Invest. 2005 Nov;52 Suppl:284-90. [PubMed:16366516]
  2. 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. [PubMed:9083792]
  3. 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. [PubMed:16925992]
  4. 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. [PubMed:16981227]
  5. Wood M, Reavill C: Aripiprazole acts as a selective dopamine D2 receptor partial agonist. Expert Opin Investig Drugs. 2007 Jun;16(6):771-5. [PubMed:17501690]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Partial agonist
General Function
Serotonin receptor activity
Specific 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...
Gene Name
HTR1A
Uniprot ID
P08908
Uniprot Name
5-hydroxytryptamine receptor 1A
Molecular Weight
46106.335 Da
References
  1. 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. [PubMed:12063084]
  2. 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. [PubMed:14647959]
  3. 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. [PubMed:14709325]
  4. Swainston Harrison T, Perry CM: Aripiprazole: a review of its use in schizophrenia and schizoaffective disorder. Drugs. 2004;64(15):1715-36. [PubMed:15257633]
  5. 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. [PubMed:15862515]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
References
  1. 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. [PubMed:14642974]
  2. 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. [PubMed:17242925]
  3. 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. [PubMed:17265076]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
Gene Name
HTR1B
Uniprot ID
P28222
Uniprot Name
5-hydroxytryptamine receptor 1B
Molecular Weight
43567.535 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
Gene Name
HTR1D
Uniprot ID
P28221
Uniprot Name
5-hydroxytryptamine receptor 1D
Molecular Weight
41906.38 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. Ligand binding causes a conformation change that trig...
Gene Name
HTR1E
Uniprot ID
P28566
Uniprot Name
5-hydroxytryptamine receptor 1E
Molecular Weight
41681.57 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name
DRD1
Uniprot ID
P21728
Uniprot Name
D(1A) dopamine receptor
Molecular Weight
49292.765 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name
DRD5
Uniprot ID
P21918
Uniprot Name
D(1B) dopamine receptor
Molecular Weight
52950.5 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
G-protein coupled amine receptor activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
Gene Name
DRD3
Uniprot ID
P35462
Uniprot Name
D(3) dopamine receptor
Molecular Weight
44224.335 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Curator comments
Aripiprazole displays moderate affinity toward the receptor with a moderate affinity and Ki of 44 nM.
General Function
Sh3 domain binding
Specific 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. Its activity is mediated by G proteins ...
Gene Name
DRD4
Uniprot ID
P21917
Uniprot Name
D(4) dopamine receptor
Molecular Weight
48359.86 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Curator comments
Aripiprazole displays moderate affinity toward the receptor with a moderate affinity and Ki of 15 nM.
General Function
Serotonin receptor activity
Specific 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-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51820.705 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Voltage-gated potassium channel activity
Specific 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. This receptor is a ligand-gate...
Gene Name
HTR3A
Uniprot ID
P46098
Uniprot Name
5-hydroxytryptamine receptor 3A
Molecular Weight
55279.835 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Serotonin receptor activity
Specific 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 ...
Gene Name
HTR6
Uniprot ID
P50406
Uniprot Name
5-hydroxytryptamine receptor 6
Molecular Weight
46953.625 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Curator comments
Aripiprazole displays moderate affinity toward the receptor with a moderate affinity and Ki of 39 nM.
General Function
Serotonin receptor activity
Specific 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 ...
Gene Name
HTR7
Uniprot ID
P34969
Uniprot Name
5-hydroxytryptamine receptor 7
Molecular Weight
53554.43 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
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
Histamine receptor activity
Specific 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 catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
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
Protein heterodimerization activity
Specific 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) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
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
Protein heterodimerization activity
Specific 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) prot...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
Pharmacological action
No
General Function
Thioesterase binding
Specific 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 oxymetazo...
Gene Name
ADRA2A
Uniprot ID
P08913
Uniprot Name
Alpha-2A adrenergic receptor
Molecular Weight
48956.275 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
Pharmacological action
No
General Function
Epinephrine binding
Specific 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...
Gene Name
ADRA2B
Uniprot ID
P18089
Uniprot Name
Alpha-2B adrenergic receptor
Molecular Weight
49565.8 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
Pharmacological action
No
General Function
Protein homodimerization activity
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name
ADRA2C
Uniprot ID
P18825
Uniprot Name
Alpha-2C adrenergic receptor
Molecular Weight
49521.585 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
Pharmacological action
No
Curator comments
According to the FDA label, aripiprazole has no appreciable affinity for cholinergic muscarinic receptors (IC50>1000 nM).
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
Pharmacological action
No
Curator comments
According to the FDA label, aripiprazole has no appreciable affinity for cholinergic muscarinic receptors (IC50>1000 nM).
General Function
G-protein coupled acetylcholine receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
Pharmacological action
No
Curator comments
IC50 is >1000 nM.
General Function
Receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM3
Uniprot ID
P20309
Uniprot Name
Muscarinic acetylcholine receptor M3
Molecular Weight
66127.445 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
Pharmacological action
No
Curator comments
According to the FDA label, aripiprazole has no appreciable affinity for cholinergic muscarinic receptors (IC50>1000 nM).
General Function
Guanyl-nucleotide exchange factor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM4
Uniprot ID
P08173
Uniprot Name
Muscarinic acetylcholine receptor M4
Molecular Weight
53048.65 Da
References
  1. 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. [PubMed:17848919]
Kind
Protein
Organism
Human
Pharmacological action
No
Curator comments
According to the FDA label, aripiprazole has no appreciable affinity for cholinergic muscarinic receptors (IC50>1000 nM).
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM5
Uniprot ID
P08912
Uniprot Name
Muscarinic acetylcholine receptor M5
Molecular Weight
60073.205 Da
References
  1. 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. [PubMed:17848919]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da

Drug created on July 03, 2018 11:32 / Updated on November 02, 2018 07:51