brexpiprazole Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
psychotropics, phenylpiperazine derivatives 5014 913611-97-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • brexpiprazole
  • rexulti
  • OPC-34712
  • OPC 34712
an atypical antipsychotic the efficacy of brexpiprazole may be mediated through a combination of partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors
  • Molecular weight: 433.57
  • Formula: C25H27N3O2S
  • CLOGP: 4.65
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 1
  • TPSA: 44.81
  • ALOGS: -5.28
  • ROTB: 7

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
3 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Hosey CM, Chan R, Benet LZ
Vd (Volume of distribution) 1.46 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.34 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.00 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 54.37 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
July 27, 2018 EMA OTSUKA PHARM CO LTD
Jan. 19, 2018 PMDA Otsuka Pharmaceutical Co., Ltd.
July 10, 2015 FDA OTSUKA PHARM CO LTD

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Akathisia 385.15 27.86 96 3846 7618 46674502
Weight increased 298.61 27.86 180 3762 164293 46517827
Off label use 222.73 27.86 211 3731 379630 46302490
Restlessness 106.51 27.86 49 3893 25475 46656645
Tardive dyskinesia 94.10 27.86 32 3910 7511 46674609
Schizoaffective disorder 92.36 27.86 22 3920 1430 46680690
Inability to afford medication 80.97 27.86 19 3923 1157 46680963
Product administered to patient of inappropriate age 78.85 27.86 22 3920 2674 46679446
Suicidal ideation 77.37 27.86 52 3890 56330 46625790
Mania 75.70 27.86 30 3912 10816 46671304
Product use in unapproved indication 65.62 27.86 57 3885 90216 46591904
Sinus rhythm 48.16 27.86 11 3931 594 46681526
Anxiety 47.37 27.86 67 3875 181890 46500230
Anger 43.97 27.86 21 3921 11831 46670289
Depression 43.33 27.86 62 3880 170042 46512078
Wrong technique in product usage process 42.83 27.86 36 3906 54386 46627734
Tremor 41.64 27.86 50 3892 115589 46566531
Drug level increased 37.87 27.86 22 3920 18419 46663701
Adverse event 36.33 27.86 27 3915 34157 46647963
Eye movement disorder 36.04 27.86 14 3928 4779 46677341
Extrapyramidal disorder 35.91 27.86 18 3924 11250 46670870
Food craving 31.59 27.86 9 3933 1178 46680942
Insomnia 30.62 27.86 52 3890 164872 46517248
Compulsive shopping 30.32 27.86 8 3934 787 46681333
Feeling abnormal 29.50 27.86 44 3898 125016 46557104
Sedation 28.69 27.86 20 3922 22890 46659230
Electrocardiogram QT prolonged 28.65 27.86 28 3914 51297 46630823
Increased appetite 28.29 27.86 14 3928 8513 46673607

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Akathisia 223.97 36.67 54 1575 5850 29944999
Off label use 107.61 36.67 96 1533 249194 29701655
Weight increased 98.33 36.67 57 1572 74856 29875993
Product administered to patient of inappropriate age 74.78 36.67 19 1610 2524 29948325
Tardive dyskinesia 66.13 36.67 20 1609 5037 29945812
Restlessness 57.85 36.67 27 1602 22572 29928277
Suicidal ideation 51.27 36.67 29 1600 36085 29914764
Anxiety 49.36 36.67 40 1589 89831 29861018
No adverse event 48.28 36.67 22 1607 17397 29933452
Schizophrenia 40.27 36.67 16 1613 9032 29941817
Inability to afford medication 39.23 36.67 9 1620 776 29950073
Apathy 38.49 36.67 14 1615 6218 29944631

Pharmacologic Action:

SourceCodeDescription
ATC N05AX16 NERVOUS SYSTEM
PSYCHOLEPTICS
ANTIPSYCHOTICS
Other antipsychotics
FDA EPC N0000175430 Atypical Antipsychotic
MeSH PA D015259 Dopamine Agents
MeSH PA D018491 Dopamine Agonists
MeSH PA D018377 Neurotransmitter Agents
MeSH PA D018490 Serotonin Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Schizophrenia indication 58214004 DOID:5419
Major depressive disorder indication 370143000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 12.14 acidic
pKa2 8.07 Basic
pKa3 0.9 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
D(2) dopamine receptor GPCR AGONIST Ki 9.52 SCIENTIFIC LITERATURE DRUG LABEL
5-hydroxytryptamine receptor 1A GPCR AGONIST Ki 9.92 SCIENTIFIC LITERATURE DRUG LABEL
5-hydroxytryptamine receptor 2A GPCR ANTAGONIST Ki 9.33 SCIENTIFIC LITERATURE DRUG LABEL
5-hydroxytryptamine receptor 2C GPCR Ki 7.47 SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 5A GPCR Ki 6.85 SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 6 GPCR Ki 7.24 SCIENTIFIC LITERATURE
Alpha-1A adrenergic receptor GPCR Ki 8.42 SCIENTIFIC LITERATURE
Alpha-2A adrenergic receptor GPCR Ki 7.82 SCIENTIFIC LITERATURE
Alpha-2B adrenergic receptor GPCR Ki 7.77 SCIENTIFIC LITERATURE
Beta-1 adrenergic receptor GPCR Ki 7.23 SCIENTIFIC LITERATURE
Beta-2 adrenergic receptor GPCR Ki 7.17 SCIENTIFIC LITERATURE
Sodium-dependent serotonin transporter Transporter INHIBITOR IC50 7.54 SCIENTIFIC LITERATURE
Sodium-dependent noradrenaline transporter Transporter INHIBITOR IC50 6.86 SCIENTIFIC LITERATURE
Sodium-dependent dopamine transporter Transporter INHIBITOR IC50 6.02 SCIENTIFIC LITERATURE
D(3) dopamine receptor GPCR AGONIST Ki 8.96 SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 2B GPCR ANTAGONIST Ki 8.72 SCIENTIFIC LITERATURE
Alpha-1B adrenergic receptor GPCR ANTAGONIST Ki 9.77 SCIENTIFIC LITERATURE
Alpha-2C adrenergic receptor GPCR ANTAGONIST Ki 9.23 SCIENTIFIC LITERATURE
Histamine H1 receptor GPCR ANTAGONIST Ki 7.72 SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 7 GPCR ANTAGONIST Ki 8.43 SCIENTIFIC LITERATURE
D(1A) dopamine receptor GPCR AGONIST Ki 6.80 SCIENTIFIC LITERATURE
Alpha-1D adrenergic receptor GPCR ANTAGONIST Ki 8.59 SCIENTIFIC LITERATURE
D(4) dopamine receptor GPCR AGONIST Ki 8.20 SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 1B GPCR Ki 7.49 SCIENTIFIC LITERATURE

External reference:

IDSource
2J3YBM1K8C UNII
D10309 KEGG_DRUG
4034625 VUID
N0000191737 NUI
4034625 VANDF
C3885614 UMLSCUI
CHEBI:134716 CHEBI
CHEMBL2105760 ChEMBL_ID
DB09128 DRUGBANK_ID
9552 INN_ID
C000591922 MESH_SUPPLEMENTAL_RECORD_UI
11978813 PUBCHEM_CID
7672 IUPHAR_LIGAND_ID
1658314 RXNORM
234913 MMSL
31120 MMSL
d08373 MMSL
016270 NDDF
716069007 SNOMEDCT_US
781292006 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Rexulti HUMAN PRESCRIPTION DRUG LABEL 1 59148-035 TABLET 0.25 mg ORAL NDA 37 sections
Rexulti HUMAN PRESCRIPTION DRUG LABEL 1 59148-036 TABLET 0.50 mg ORAL NDA 37 sections
Rexulti HUMAN PRESCRIPTION DRUG LABEL 1 59148-037 TABLET 1 mg ORAL NDA 37 sections
Rexulti HUMAN PRESCRIPTION DRUG LABEL 1 59148-038 TABLET 2 mg ORAL NDA 37 sections
Rexulti HUMAN PRESCRIPTION DRUG LABEL 1 59148-039 TABLET 3 mg ORAL NDA 37 sections
Rexulti HUMAN PRESCRIPTION DRUG LABEL 1 59148-040 TABLET 4 mg ORAL NDA 37 sections