U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C28H36N4O2S
Molecular Weight 492.6782
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LURASIDONE

SMILES

C1CC[C@@]([H])(CN2C(=O)[C@]3([H])[C@@]4([H])CC[C@]([H])(C4)[C@]3([H])C2=O)[C@@]([H])(C1)CN5CCN(CC5)c6c7ccccc7sn6

InChI

InChIKey=PQXKDMSYBGKCJA-CVTJIBDQSA-N
InChI=1S/C28H36N4O2S/c33-27-24-18-9-10-19(15-18)25(24)28(34)32(27)17-21-6-2-1-5-20(21)16-30-11-13-31(14-12-30)26-22-7-3-4-8-23(22)35-29-26/h3-4,7-8,18-21,24-25H,1-2,5-6,9-17H2/t18-,19+,20-,21-,24+,25-/m0/s1

HIDE SMILES / InChI

Molecular Formula C28H36N4O2S
Molecular Weight 492.6782
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 6 / 6
E/Z Centers 0
Optical Activity UNSPECIFIED

Lurasidone is a novel antipsychotic agent approved for the treatment of schizophrenia in a number of countries including the UK and is also approved in the USA and Canada for the treatment of bipolar depression as either a monotherapy or adjunctive therapy with lithium or valproate. In addition, lurasidone is in phase III of a clinical trial for the treatment patient with major depressive disorder and for the treatment of irritability associated with autistic disorder. The mechanism of action of lurasidone, as with other drugs having efficacy in schizophrenia, is unknown but is known, that lurasidone has a high affinity for dopamine D2, serotonin 5-HT2A and serotonin 5-HT7 receptors where it has antagonist effects. In addition, lurasidone is a partial agonist at the serotonin 5-HT1A receptor and has no appreciable affinity for histamine or muscarinic receptors.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P14416
Gene ID: 1813
Gene Symbol: DRD2
Target Organism: Homo sapiens (Human)
1 nM [Ki]
Target ID: P28223
Gene ID: 3356
Gene Symbol: HTR2A
Target Organism: Homo sapiens (Human)
0.5 nM [Ki]
Target ID: P34969
Gene ID: 3363
Gene Symbol: HTR7
Target Organism: Homo sapiens (Human)
0.5 nM [Ki]
Target ID: P08908
Gene ID: 3350
Gene Symbol: HTR1A
Target Organism: Homo sapiens (Human)
6.40000000000000036 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
LATUDA

Approved Use

LATUDA is an atypical antipsychotic agent indicated for the treatment of patients with schizophrenia.

Launch Date

1288224000000
Primary
LATUDA

Approved Use

(Latuda, Sunovion Pharmaceuticals), already indicated for schizophrenia, to treat major depressive episodes in adults with bipolar 1 disorder.

Launch Date

1288224000000
Primary
Primary
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
38.4 ng/mL
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LURASIDONE plasma
Homo sapiens
population: UNHEALTHY
age: ADOLESCENT
sex: FEMALE / MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
153 ng × h/mL
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LURASIDONE plasma
Homo sapiens
population: UNHEALTHY
age: ADOLESCENT
sex: FEMALE / MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
21.3 h
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LURASIDONE plasma
Homo sapiens
population: UNHEALTHY
age: ADOLESCENT
sex: FEMALE / MALE
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LURASIDONE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
600 mg 1 times / day multiple, oral
Highest studied dose
unhealthy, 42
400 mg 1 times / day multiple, oral
MTD
unhealthy, 42
560 mg single, oral
Overdose
Dose: 560 mg
Route: oral
Route: single
Dose: 560 mg
Sources:
unhealthy
120 mg 1 times / day multiple, oral
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Dystonia...
AEs leading to
discontinuation/dose reduction:
Dystonia
Sources:
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Cerebrovascular disorder (NOS), Neuroleptic malignant syndrome...
AEs leading to
discontinuation/dose reduction:
Cerebrovascular disorder (NOS)
Neuroleptic malignant syndrome
Tardive dyskinesia
Hyperglycemia
Diabetes mellitus
Dyslipidemia
Weight gain
Hyperprolactinemia
Leukopenia
Neutropenia
Agranulocytosis
Orthostatic hypotension
Syncope
Suicidal behavior
Sources:
AEs

AEs

AESignificanceDosePopulation
Dystonia Disc. AE
120 mg 1 times / day multiple, oral
Recommended
Dose: 120 mg, 1 times / day
Route: oral
Route: multiple
Dose: 120 mg, 1 times / day
Sources:
unhealthy
Agranulocytosis Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy
Cerebrovascular disorder (NOS) Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy
Diabetes mellitus Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy
Dyslipidemia Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy
Hyperglycemia Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy
Hyperprolactinemia Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy
Leukopenia Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy
Neuroleptic malignant syndrome Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy
Neutropenia Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy
Orthostatic hypotension Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy
Suicidal behavior Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy
Syncope Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy
Tardive dyskinesia Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy
Weight gain Disc. AE
160 mg 1 times / day multiple, oral
Recommended
Dose: 160 mg, 1 times / day
Route: oral
Route: multiple
Dose: 160 mg, 1 times / day
Sources:
unhealthy
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
moderate [IC50 16 uM]
moderate [IC50 21 uM]
moderate [IC50 22 uM]
yes (co-administration study)
Comment: Human liver microsomes (testosterone 6b-hydroxylation), Competitive inhibitor; Coadministration of Lurasidone (120 mg on Day 6 & Days 7-12) increased Midazolam (CYP3A4 substrate, 5 mg on Days 1 &6, day 13) AUC0-24 by 17.95% (single dose), 37.92% (steady-state), AUCinf by 19.82% (SD), 43.87% (SS) and Cmax by 4.93% (SD), 21.47% (SS).,
Page: 6,15,76, (ClinPharm) 9, 38, 52, 53-54, (PMDA_I106_1) 19
moderate [IC50 5.9 uM]
moderate [IC50 6.3 uM]
moderate [IC50 6.3 uM]
moderate [IC50 7.4 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >10 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
unlikely
unlikely
unlikely
weak [IC50 30 uM]
weak [IC50 35 uM]
weak [IC50 37 uM]
weak [IC50 83 uM]
weak [IC50 90 uM]
weak [IC50 >100 uM]
weak [IC50 >100 uM]
yes [IC50 0.498 uM]
yes [IC50 0.767 uM]
yes [IC50 1 uM]
likely (co-administration study)
Comment: MDR1-LLC-PK cells (digoxin transportation); Coadministration of Lurasidone (120 mg on Days 6-13) increased Digoxin (0.25 mg on Days 1 & 13) AUC0-24 by 13.15%, AUClast by 10.53% and Cmax by 9.42%.
Page: 79, (ClinPharm) 52, 53-54
yes [IC50 1.21 uM]
yes [IC50 1.39 uM]
yes [IC50 2.57 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
yes (co-administration study)
Comment: Human CYP-expressed microsomes, Vmax = 102 pmol/min/mg; The metabolism of lurasidone in vitro (Human liver microsomes) was markedly reduced by ketoconazole (CYP3A4 inhibitor), as compared with quinidine (CYP2D6 inhibitor) and cimetidine (CYP3A4/CYP2D6 inhibitor).; Ketoconazole (strong CYP3A4 inhibitor, 400 mg on Days 7-13) increased lurasidone (10 mg on Days 1 & 11) AUClast and Cmax by 795% and 592%, respectively when they are coadministered together. Diltiazem (moderate CYP3A4 inhibitor, 240 mg on Days 1-7) increased lurasidone (20 mg on Day 5) AUCinf and Cmax by 116% and 110%, respectively when lurasidone is coadministered with diltiazem. Rifampin (strong CYP3A4 inducer, 600 mg on Days 1-8) decreased lurasidone (40 mg on Day 8) AUCinf and Cmax by 83% and 85%, respectively.
Page: 6, 15, 57, 78-79, (ClinPharm) 7, 52, 55-56, (PMDA_I106_1) 14
major
yes (co-administration study)
Comment: Human CYP-expressed microsomes, Remaining ID-14283 = 2.9% (0.5 mcg/mL, 5 min, 50 pmol/0.5mg protein/mL); Coadministration of Dilthiazem (moderate CYP 3A4 inhibitor, 240 mg on Days 1-7) increased ID-14823 (Lurasidon, 20 mg on Day 5) AUCinf by 138% and Cmax by 114%. Coadministration of Refampicin (strong CYP3A4 inducer, 600 mg on Days 1-8) decreased ID14283 (Lurasidone, 40 mg on Day 8) AUCinf by 93% and Cmac by 90%.
Page: (ClinPharm) 56, (PMDA_I106_1) 16
minor
no
no
no
no
no
no
no
yes
yes
yes
yes
yes
yes
yes
yes
yes
Tox targets
PubMed

PubMed

TitleDatePubMed
Evaluation of dopamine D₂/D₃ and serotonin 5-HT₂A receptor occupancy for a novel antipsychotic, lurasidone, in conscious common marmosets using small-animal positron emission tomography.
2013 Jan
Patents

Patents

Sample Use Guides

The recommended starting dose of LATUDA ((LURASIDONE HCL) is 40 mg once daily. LATUDA has been shown to be effective in a dose range of 40 mg/day to 120 mg/day. In the 6-week controlled trials, there was no suggestion of added benefit with the 120 mg/day dose, but there was a dose -related increase in certain adverse reactions. Therefore, the maximum recommended dose is 80 mg/day
Route of Administration: Oral
[35S]GTPγS binding experiments for the human dopamine D2L or 5-HT1A receptors stably expressed in the membranes of recombinant Chinese hamster ovary (CHO) cells were performed. After dopamine (or serotonin) and/or lurasidone were incubated for 20 min at room temperature with the cell membrane preparation containing [35S]GTPγS (0.05 nM for D2L or 0.2 nM for 5-HT1A), the membranes were filtered through glass filters and the radioactivity bound to each filter was measured with a liquid scintillation counter. For nonspecific binding, cold GTPγS (20 μM for D2L or 10 μM for 5-HT1A) was added with [35S]GTPγS. in vitro receptor binding experiments revealed that lurasidone demonstrates affinity for dopamine D2 and 5-HT2A receptors higher than other tested antipsychotics. In contrast to other agents, lurasidone also displayed high affinity for 5-HT7, 5-HT1A, and noradrenaline α2C receptors.
Substance Class Chemical
Created
by admin
on Sat Jun 26 05:34:08 UTC 2021
Edited
by admin
on Sat Jun 26 05:34:08 UTC 2021
Record UNII
22IC88528T
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LURASIDONE
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
LURASIDONE [VANDF]
Common Name English
LURASIDONE [MI]
Common Name English
LATUDA
Brand Name English
LURASIDONE [WHO-DD]
Common Name English
LURASIDONE [INN]
Common Name English
Classification Tree Code System Code
LIVERTOX 578
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
NCI_THESAURUS C66885
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
WHO-ATC N05AE05
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
WHO-VATC QN05AE05
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
EMA ASSESSMENT REPORTS LATUDA (AUTHORIZED: SCHIZOPHRENIA)
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
NDF-RT N0000175430
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
NCI_THESAURUS C66883
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
Code System Code Type Description
RXCUI
1040028
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
PRIMARY RxNorm
LACTMED
Lurasidone
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
PRIMARY
ChEMBL
CHEMBL1237021
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
PRIMARY
PUBCHEM
213046
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
PRIMARY
IUPHAR
7461
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
PRIMARY
EVMPD
SUB32185
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
PRIMARY
NCI_THESAURUS
C77575
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
PRIMARY
WIKIPEDIA
Lurasidone
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
PRIMARY
DRUG BANK
DB08815
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
PRIMARY
CAS
367514-87-2
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
PRIMARY
INN
8247
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
PRIMARY
FDA UNII
22IC88528T
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
PRIMARY
DRUG CENTRAL
4168
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
PRIMARY
MESH
C525644
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
PRIMARY
MERCK INDEX
M6943
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
PRIMARY Merck Index
HSDB
8228
Created by admin on Sat Jun 26 05:34:09 UTC 2021 , Edited by admin on Sat Jun 26 05:34:09 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
cell:CHO; ligand: 3-H-KETASERIN
BINDING
Ki
METABOLIC ENZYME -> INHIBITOR
MODERATE
METABOLIC ENZYME -> INHIBITOR
MODERATE
EXCRETED UNCHANGED
Total excretion of the dose recovered in urine and feces combined was 89.3%, with 80.1% recovered in feces and 9.2% in urine
FECAL; URINE
TARGET -> AGONIST
TARGET -> INHIBITOR
Cell:SF9; ligand:3H-5-ct
BINDING
Ki
METABOLIC ENZYME -> INHIBITOR
MODERATE
METABOLIC ENZYME -> INHIBITOR
MODERATE
BINDER->LIGAND
BINDING
TRANSPORTER -> NON-SUBSTRATE
METABOLIC ENZYME -> INHIBITOR
MODERATE
METABOLIC ENZYME -> SUBSTRATE
MAJOR
TARGET -> INHIBITOR
cell:CHO K1; ligand:3H-spiperone
Ki
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IMPURITY -> PARENT
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC single dose administration

Biological Half-life PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC single dose administration

Tmax PHARMACOKINETIC multiple dose administration

Volume of Distribution PHARMACOKINETIC single dose administration