ARIPIPRAZOLE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H27Cl2N3O2
Molecular Weight	448.385
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

ClC1=CC=CC(N2CCN(CCCCOC3=CC=C4CCC(=O)NC4=C3)CC2)=C1Cl

InChI

InChIKey=CEUORZQYGODEFX-UHFFFAOYSA-N

InChI=1S/C23H27Cl2N3O2/c24-19-4-3-5-21(23(19)25)28-13-11-27(12-14-28)10-1-2-15-30-18-8-6-17-7-9-22(29)26-20(17)16-18/h3-6,8,16H,1-2,7,9-15H2,(H,26,29)

HIDE SMILES / InChI

Molecular Formula	C23H27Cl2N3O2
Molecular Weight	448.385
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

Aripiprazole is the first next-generation atypical antipsychotic. The unique actions of aripiprazole in humans are likely a combination of "functionally selective" activation of D(2) (and possibly D(3))-dopamine receptors and serotonin 5-HT(1A) receptors, coupled with inhibition of 5-HT(2A) receptors. Aripiprazole was approved by FDA (Abilify trade name) for the treatment of schizophrenia; manic and mixed episodes associated with bipolar I disorder; major depressive disorder; irritability associated with autistic disorder; Tourette’s disorder and agitation associated with schizophrenia or bipolar mania.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Dopamine D2 receptor 297	Partial Agonist 290	0.34 nM [Ki]
Serotonin 2a (5-HT2a) receptor 231	Antagonist 2,778	8.7 nM [Ki]
Serotonin 1a (5-HT1a) receptor 172	Partial Agonist 290	5.6 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Schizophrenia 298	Primary	Approved 8,429	ABILIFY
Bipolar I disorder 17	Primary	Approved 8,429	ABILIFY
Major depressive disorder 173	Primary	Approved 8,429	ABILIFY
Autism 19	Primary	Approved 8,429	ABILIFY
Tourette's syndrome 20	Primary	Approved 8,429	ABILIFY
Agitation associated with schizophrenia or bipolar mania 4	Primary	Approved 8,429	ABILIFY

C_max

Value	Dose	Co-administered	Analyte	Population
163 ng/mL	10 mg 1 times / day multiple, oral		ARIPIPRAZOLE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
2947 ng × h/mL	10 mg 1 times / day multiple, oral		ARIPIPRAZOLE plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
52.9 h	10 mg 1 times / day multiple, oral		ARIPIPRAZOLE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
1%	10 mg 1 times / day multiple, oral		ARIPIPRAZOLE plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
30 mg 1 times / day multiple, oral Highest studied dose	unhealthy, 10-17 years n = 6	Other AEs: Abdominal pain upper, Vomiting...
2 mg single, intravenous	healthy, 35 years (range: 18-45 years) n = 16
45 mg single, intramuscular Highest studied dose	unhealthy, 39 years (range: 18-65 years) n = 4
195 mg single, oral Overdose	unhealthy, < 12 years n = 10	Other AEs: Vomiting, Somnolence...
10 mg 1 times / day steady, oral	unhealthy, adolescent n = 100	Other AEs: Extrapyramidal disorder, Neuroleptic malignant syndrome...

Showing 1 to 5 of 13 entries

Previous1 2 3Next

AEs

Show entries

AE	Significance	Dose	Population
Abdominal pain upper	17%	30 mg 1 times / day multiple, oral Highest studied dose	unhealthy, 10-17 years n = 6
Dizziness	17%	30 mg 1 times / day multiple, oral Highest studied dose	unhealthy, 10-17 years n = 6
Somnolence	17%	30 mg 1 times / day multiple, oral Highest studied dose	unhealthy, 10-17 years n = 6
Vomiting	17%	30 mg 1 times / day multiple, oral Highest studied dose	unhealthy, 10-17 years n = 6
Sedation	33%	30 mg 1 times / day multiple, oral Highest studied dose	unhealthy, 10-17 years n = 6

Showing 1 to 5 of 147 entries

Previous1 2 3 4 5…30Next

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,737 inhibitor 1,587	substrate 1,037 inhibitor 1,767	substrate 1,217 inhibitor 1,852	inhibitor 1,612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1,524 CYP2C19 1,478 P-gp 1,461 BCRP 699	CYP1A1 349 CYP1A2 1,054 CYP2A6 543 CYP2B6 664 CYP2C8 693 CYP2C19 991 CYP2E1 667 UGT 192 P-gp 1,537

Drug as perpetrator

Show entries

Target	Modality	Activity	Clinical evidence
CYP2C19 1,553	inhibitor 3,277	not significant	unlikely (co-administration study)
CYP2C9 1,819	inhibitor 3,277	not significant	unlikely (co-administration study)
CYP2D6 1,891	inhibitor 3,277	not significant	unlikely (co-administration study)
CYP3A4 1,925	inhibitor 3,277	not significant	unlikely (co-administration study)
CYP1A2 1,692	inhibitor 3,277	not significant	unlikely

Showing 1 to 5 of 7 entries

Previous1 2Next

Drug as victim

Show entries

Target	Modality	Activity
CYP1A1 349	substrate 3,367	no
CYP1A2 1,054	substrate 3,367	no
CYP2A6 543	substrate 3,367	no
CYP2B6 664	substrate 3,367	no
CYP2C19 991	substrate 3,367	no

Showing 1 to 5 of 12 entries

Previous1 2 3Next

Tox targets

Show entries

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1,647	inhibitor 1,626

Showing 1 to 1 of 1 entries

Previous1Next

Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:31236	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:31236
ChemicalBook	CB42487193	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB42487193
ChemicalBook	CB8210870	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8210870
MolPort	MolPort-002-885-808	https://www.molport.com/shop/molecule-link/MolPort-002-885-808
MolPort	MolPort-046-939-776	https://www.molport.com/shop/molecule-link/MolPort-046-939-776

Showing 1 to 5 of 8 entries

Previous1 2Next

PubMed

Show entries

Title	Date	PubMed
Nonconserved residues in the second transmembrane-spanning domain of the D(4) dopamine receptor are molecular determinants of D(4)-selective pharmacology.	2000 Jan	10617689
Gateways to clinical trials.	2002 Dec	12616965
Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors.	2002 Jul	12065741
Biological perspectives. Aripiprazole: a third generation of antipsychotics begins?	2002 Oct-Dec	12629954
The psychopharmacology of ziprasidone: receptor-binding properties and real-world psychiatric practice.	2003	14728084

Showing 1 to 5 of 21 entries

Previous1 2 3 4 5Next

Patents

Sample Use Guides

In Vivo Use Guide

In adults with schizophrenia the recommended starting and target dose for aripiprazole (ABILIFY) is 10 or 15 mg/day. In adolescents the target dose is 10 mg/day. In adults with Bipolar I Disorder, the recommended starting dose is 15 mg given once daily as monotherapy and 10 mg to 15 mg given once daily as adjunctive therapy with lithium or valproate. In pediatric patients (10 to 17 years) with Bipolar I Disorder, the starting dose as monotherapy is 2 mg/day, with titration to 5 mg/day after 2 days, and a target dose of 10 mg/day after 2 additional days. In adults with Major Depressive Disorder, the recommended starting dose as adjunctive treatment for patients already taking an antidepressant is 2 to 5 mg/day. The recommended dosage range is 2 to 15 mg/day. In pediatric patients with Irritability Associated with Autistic Disorder, dosing should be initiated at 2 mg/day. The dose should be increased to 5 mg/day, with subsequent increases to 10 or 15 mg/day if needed. In pediatric patient with Tourette’s Disorder, the recommended dosage is 5 to 20 mg/day. In adults with Agitation Associated with Schizophrenia or Bipolar Mania, the recommended dose is 9.75 mg. The recommended dosage range is 5.25 to 15 mg.

Route of Administration: Other

In Vitro Use Guide

PC12 cells were treated with 0.001-1.0 uM aripiprazole in the presence of NGF (2.5ng/ml). Aripiprazole significantly potentiated nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells, in a concentration-dependent manner.

Substance Class	Chemical
Record UNII	82VFR53I78
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

ARIPIPRAZOLE

Official Name

English

ARIPIPRAZOLE [USAN]

Common Name

English

ARIPIPRAZOLE [USP MONOGRAPH]

Common Name

English

ABILIFY MYCITE

Brand Name

English

ABILIFY MAINTENA

Brand Name

English

Showing 1 to 5 of 24 entries

Previous1 2 3 4 5Next

Show entries

Classification Tree

Code System

Code

Agent Affecting Nervous System

NCI_THESAURUS

C29710

Designated/Approved

FDA ORPHAN DRUG

207905

AFFECTIVE DISORDERS, PSYCHOTIC

EMA ASSESSMENT REPORTS

ABILIFY (AUTHORIZED: BIPOLAR DISORDER)

Antipsychotic

LIVERTOX

NBK547858

SCHIZOPHRENIA AND DISORDERS WITH PSYCHOTIC FEATURES

EMA ASSESSMENT REPORTS

ABILIFY MAINTENA (AUTHORIZED: SCHIZOPHRENIA)

Showing 1 to 5 of 10 entries

Previous1 2Next

Show entries

Code System

Code

Type

Description

HSDB

7320

PRIMARY

WIKIPEDIA

ARIPIPRAZOLE

PRIMARY

LACTMED

Aripiprazole

PRIMARY

DAILYMED

82VFR53I78

PRIMARY

MERCK INDEX

m2046

PRIMARY

Merck Index

Showing 1 to 5 of 23 entries

Previous1 2 3 4 5Next

Show entries

Related Record

Type

Details


					G9XQ9S7T2F

D(3) DOPAMINE RECEPTOR

TARGET->PARTIAL AGONIST

Qualification:

Ki

Amount:

1 NANOMOLAR [0.6 to 1.4] (average)


					UKK18ES9TF

5-HYDROXYTRYPTAMINE RECEPTOR 1A

TARGET->PARTIAL AGONIST

Qualification:

Ki

Amount:

5.6 NANOMOLAR [4.8 to 6.4] (average)


					6D53G0FD0Z

PLASMA PROTEIN FRACTION (HUMAN)

BINDER->LIGAND

Interaction Type:

BINDING

Amount:

[>99] % (average)


					82VFR53I78

ARIPIPRAZOLE

EXCRETED UNCHANGED

Qualification:

FECAL

Amount:

[8 to 18] % (average)


					19GBD6T9L7

D(2) DOPAMINE RECEPTOR

TARGET->PARTIAL AGONIST

Qualification:

Ki

Amount:

0.8 NANOMOLAR [0.7 to 0.9] (average)

Showing 1 to 5 of 18 entries

Previous1 2 3 4Next

Show entries

Related Record

Type

Details


					UEY2TJ7FPV

7-(4-HYDROXYBUTOXY)-3,4-DIHYDROQUINOLIN-2(1H)-ONE

METABOLITE -> PARENT

Qualification:

URINE

Amount:

1 % (average)


					UK756P561X

2,3-DICHLORO-4-PIPERAZIN-1-YL-PHENOL

METABOLITE -> PARENT

Qualification:

URINE

Amount:

5 % (average)


					2S514OZH3B

DEHYDROARIPIPRAZOLE

METABOLITE ACTIVE -> PARENT

Interaction Type:

MAJOR

Qualification:

PLASMA

Amount:

MOLE PERCENT OF AMOUNT ADMINISTERED 20 % (average)
of the total radioactivity


					16D0X6IIWJ

OPC-3952

METABOLITE -> PARENT

Qualification:

URINE

Amount:

10 % (average)


					9K3DEA9SHF

4-((2-OXO-3,4-DIHYDRO-1H-QUINOLIN-7-YL)OXY)BUTANOIC ACID

METABOLITE -> PARENT

Comments:

N-Dealkylation metabolite thru CYP3A4 exposure.

Amount:

Showing 1 to 5 of 16 entries

Previous1 2 3 4Next

Show entries

Related Record

Type

Details


					353J3NU2S8

DESCHLORO ARIPIPRAZOLE

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:

[<0.1] PERCENT PEAK AREA (limits)


					FS6X5WDG7B

ARIPIPRAZOLE DIQUINOLINE BUTANEDIOL

IMPURITY -> PARENT

Amount:


					002239IPE1

DESETHYLENE ARIPIPRAZOLE

IMPURITY -> PARENT

Amount:


					5NO9KAA6QP

ARIPIPRAZOLE N1-OXIDE

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

USP

Amount:

[<0.1] PERCENT PEAK AREA (limits)


					D9ZEV5PJY5

7,7'-((OXYBIS(BUTANE-4,1-DIYL))BIS(OXY))BIS(3,4-DIHYDROQUINOLIN-2(1H)-ONE)

IMPURITY -> PARENT

Amount:

Showing 1 to 5 of 12 entries

Previous1 2 3Next

Show entries

Related Record

Type

Details


					82VFR53I78

ARIPIPRAZOLE

ACTIVE MOIETY

Amount:

Showing 1 to 1 of 1 entries

Previous1Next

Name	Property Type	Amount
Biological Half-life	PHARMACOKINETIC	[75 to 94] hours (average)

ORAL BIOAVAILABILITY	PHARMACOKINETIC	87 % (average)

Volume of Distribution	PHARMACOKINETIC	4.9 Liters/Kilogram (average)

Tmax	PHARMACOKINETIC	[3 to 5] hours (average)

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator