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

Stem definition	Drug id	CAS RN
psychotropics, phenylpiperazine derivatives	5014	913611-97-9

Description:

Molecule

Description

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:

Dose	Unit	Route
3	mg	O

ADMET properties:

Property	Value	Reference
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:

Date	Agency	Company	Orphan
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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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:

Source	Code	Description
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)

Disease	Relation	SNOMED_ID	DOID
Schizophrenia	indication	58214004	DOID:5419
Major depressive disorder	indication	370143000

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
D(2) dopamine receptor	GPCR	P14416	DRD2_HUMAN	AGONIST	Ki	9.52		SCIENTIFIC LITERATURE	DRUG LABEL
5-hydroxytryptamine receptor 1A	GPCR	P08908	5HT1A_HUMAN	AGONIST	Ki	9.92		SCIENTIFIC LITERATURE	DRUG LABEL
5-hydroxytryptamine receptor 2A	GPCR	P28223	5HT2A_HUMAN	ANTAGONIST	Ki	9.33		SCIENTIFIC LITERATURE	DRUG LABEL
5-hydroxytryptamine receptor 2C	GPCR	P28335	5HT2C_HUMAN		Ki	7.47		SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 5A	GPCR	P47898	5HT5A_HUMAN		Ki	6.85		SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 6	GPCR	P50406	5HT6R_HUMAN		Ki	7.24		SCIENTIFIC LITERATURE
Alpha-1A adrenergic receptor	GPCR	P35348	ADA1A_HUMAN		Ki	8.42		SCIENTIFIC LITERATURE
Alpha-2A adrenergic receptor	GPCR	P08913	ADA2A_HUMAN		Ki	7.82		SCIENTIFIC LITERATURE
Alpha-2B adrenergic receptor	GPCR	P18089	ADA2B_HUMAN		Ki	7.77		SCIENTIFIC LITERATURE
Beta-1 adrenergic receptor	GPCR	P08588	ADRB1_HUMAN		Ki	7.23		SCIENTIFIC LITERATURE
Beta-2 adrenergic receptor	GPCR	P07550	ADRB2_HUMAN		Ki	7.17		SCIENTIFIC LITERATURE
Sodium-dependent serotonin transporter	Transporter	P31645	SC6A4_HUMAN	INHIBITOR	IC50	7.54		SCIENTIFIC LITERATURE
Sodium-dependent noradrenaline transporter	Transporter	P23975	SC6A2_HUMAN	INHIBITOR	IC50	6.86		SCIENTIFIC LITERATURE
Sodium-dependent dopamine transporter	Transporter	Q01959	SC6A3_HUMAN	INHIBITOR	IC50	6.02		SCIENTIFIC LITERATURE
D(3) dopamine receptor	GPCR	P35462	DRD3_HUMAN	AGONIST	Ki	8.96		SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 2B	GPCR	P41595	5HT2B_HUMAN	ANTAGONIST	Ki	8.72		SCIENTIFIC LITERATURE
Alpha-1B adrenergic receptor	GPCR	P35368	ADA1B_HUMAN	ANTAGONIST	Ki	9.77		SCIENTIFIC LITERATURE
Alpha-2C adrenergic receptor	GPCR	P18825	ADA2C_HUMAN	ANTAGONIST	Ki	9.23		SCIENTIFIC LITERATURE
Histamine H1 receptor	GPCR	P35367	HRH1_HUMAN	ANTAGONIST	Ki	7.72		SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 7	GPCR	P34969	5HT7R_HUMAN	ANTAGONIST	Ki	8.43		SCIENTIFIC LITERATURE
D(1A) dopamine receptor	GPCR	P21728	DRD1_HUMAN	AGONIST	Ki	6.80		SCIENTIFIC LITERATURE
Alpha-1D adrenergic receptor	GPCR	P25100	ADA1D_HUMAN	ANTAGONIST	Ki	8.59		SCIENTIFIC LITERATURE
D(4) dopamine receptor	GPCR	P21917	DRD4_HUMAN	AGONIST	Ki	8.20		SCIENTIFIC LITERATURE
5-hydroxytryptamine receptor 1B	GPCR	P28222	5HT1B_HUMAN		Ki	7.49		SCIENTIFIC LITERATURE

External reference:

ID	Source
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:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
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