Identification

Name
Lurasidone
Accession Number
DB08815
Type
Small Molecule
Groups
Approved, Investigational
Description

Lurasidone is an atypical antipsychotic developed by Dainippon Sumitomo Pharma. It was approved by the U.S. Food and Drug Administration (FDA) for treatment of schizophrenia on October 29, 2010 and is currently pending approval for the treatment of bipolar disorder in the United States. (Wikipedia)

Structure
Thumb
Synonyms
  • Lurasidona
  • Lurasidonum
External IDs
SM-13496
Product Ingredients
IngredientUNIICASInChI Key
Lurasidone HydrochlorideO0P4I5851I367514-88-3NEKCRUIRPWNMLK-SCIYSFAVSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LatudaTablet60 mgOralSunovion2014-03-14Not applicableCanada
LatudaTablet40 mgOralSunovion2012-09-06Not applicableCanada
LatudaTablet, film coated80 mg/1OralSunovion2010-10-28Not applicableUs63402 0308 30 nlmimage10 253d12d8
LatudaTablet, film coated20 mg/1OralSunovion2011-12-07Not applicableUs63402 0302 30 nlmimage10 113d88fc
LatudaTablet, film coated40 mg/1OralBushu Pharmaceutical, LTD.2010-10-28Not applicableUs
LatudaTablet120 mgOralSunovion2012-09-06Not applicableCanada
LatudaTablet, film coated60 mg/1OralSunovion2013-07-12Not applicableUs63402 0306 30 nlmimage10 2d3d16f8
LatudaTablet, film coated40 mg/1OralAvera McKennan Hospital2015-03-02Not applicableUs69189 031620180907 15195 1j92cxo
LatudaTablet20 mgOralSunovion2014-04-09Not applicableCanada
LatudaTablet80 mgOralSunovion2012-09-05Not applicableCanada
Categories
UNII
22IC88528T
CAS number
367514-87-2
Weight
Average: 492.676
Monoisotopic: 492.255897106
Chemical Formula
C28H36N4O2S
InChI Key
PQXKDMSYBGKCJA-CVTJIBDQSA-N
InChI
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
IUPAC Name
(1R,2S,6R,7S)-4-{[(1R,2R)-2-{[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]methyl}cyclohexyl]methyl}-4-azatricyclo[5.2.1.0²,⁶]decane-3,5-dione
SMILES
O=C1[C@H]2[C@@H]3CC[C@@H](C3)[C@H]2C(=O)N1C[C@@H]1CCCC[C@H]1CN1CCN(CC1)C1=NSC2=CC=CC=C12

Pharmacology

Indication

Treatment of schizophrenia.

Associated Conditions
Pharmacodynamics

Lurasidone is a benzothiazol derivative that is an antagonist and binds with high affinity to Dopamine-2 (D2) (Ki = 0.994 nM), 5-HT2A (Ki = 0.47 nM) receptors, and 5-HT7 receptors (Ki = 0.495 nM). It also binds with moderate affinity to alpha-2C adrenergic receptors (Ki = 10.8 nM) and is a partial agonist at 5-HT1A receptors (Ki = 6.38 nM). Its actions on histaminergic and muscarinic receptors are negligible.

Mechanism of action

Lurasidone is an atypical antipsychotic that is a D2 and 5-HT2A (mixed serotonin and dopamine activity) to improve cognition. It is thought that antagonism of serotonin receptors can improve negative symptoms of psychoses and reduce the extrapyramidal side effects that are often associated with typical antipsychotics.

TargetActionsOrganism
AD(2) dopamine receptor
antagonist
Human
A5-hydroxytryptamine receptor 2A
antagonist
Human
U5-hydroxytryptamine receptor 7
antagonist
Human
U5-hydroxytryptamine receptor 1A
antagonist
Human
UAlpha-2C adrenergic receptor
antagonist
Human
UAlpha-2A adrenergic receptorNot AvailableHuman
Absorption

Lurasidone is readily absorbed and quickly reaches maximal concentrations (Cmax) within 1-4 hours. When taken with food, there is a two-fold increase in exposure and time to maximal concentration is increased by 0.5-1.5 hours. This occurs regardless of fat or caloric content.
Bioavailability = 9-19%.

Volume of distribution

6173 L

Protein binding

~99% bound to serum proteins.

Metabolism

Lurasidone is metabolized by CYP3A4 in which its major active metabolite is referred to as ID-14283 (25% of parent exposure). Its two minor metabolites are referred to as ID14326 and ID11614 which make up 3% and 1% of parent exposure respectively. Its two non-active metabolites are referred to as ID-20219 and ID-20220.

Route of elimination

Urine (~9%) and feces (~80%)

Half life

40 mg dose= 18 hours 120 mg - 160 mg dose = 29-37 hours

Clearance

3902 mL/min

Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(1S,6R)-3-{[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]CARBONYL}-6-(2,4,5-TRIFLUOROPHENYL)CYCLOHEX-3-EN-1-AMINEThe therapeutic efficacy of (1S,6R)-3-{[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]CARBONYL}-6-(2,4,5-TRIFLUOROPHENYL)CYCLOHEX-3-EN-1-AMINE can be decreased when used in combination with Lurasidone.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Lurasidone.
2,5-Dimethoxy-4-ethylamphetamineLurasidone may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineLurasidone may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineLurasidone may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineLurasidone may decrease the stimulatory activities of 4-Bromo-2,5-dimethoxyamphetamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Lurasidone is combined with 7-Nitroindazole.
AcarboseThe therapeutic efficacy of Acarbose can be decreased when used in combination with Lurasidone.
AcepromazineThe risk or severity of adverse effects can be increased when Lurasidone is combined with Acepromazine.
AceprometazineThe risk or severity of adverse effects can be increased when Lurasidone is combined with Aceprometazine.
Food Interactions
  • When taken with food, there is a two-fold increase in exposure and time to maximal concentration is increased by 0.5-1.5 hours.

References

General References
  1. George M, Amrutheshwar R, Rajkumar RP, Kattimani S, Dkhar SA: Newer antipsychotics and upcoming molecules for schizophrenia. Eur J Clin Pharmacol. 2013 Aug;69(8):1497-509. doi: 10.1007/s00228-013-1498-4. Epub 2013 Apr 2. [PubMed:23545936]
  2. Tarazi FI, Stahl SM: Iloperidone, asenapine and lurasidone: a primer on their current status. Expert Opin Pharmacother. 2012 Sep;13(13):1911-22. doi: 10.1517/14656566.2012.712114. Epub 2012 Jul 31. [PubMed:22849428]
External Links
KEGG Drug
D04820
PubChem Compound
213046
PubChem Substance
175427100
ChemSpider
184739
BindingDB
85222
ChEBI
70735
ChEMBL
CHEMBL1237021
PharmGKB
PA166129557
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Lurasidone
ATC Codes
N05AE05 — Lurasidone
AHFS Codes
  • 28:16.08.04 — Atypical Antipsychotics
FDA label
Download (452 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableMale, Healthy Normal Subjects1
1CompletedNot AvailableMetabolism / Pharmacokinetics1
1CompletedNot AvailablePharmacokinetics1
1CompletedNot AvailableSchizophrenia Patients1
1CompletedNot AvailableSchizophrenic Disorders3
1CompletedBasic ScienceSchizophrenic Disorders1
1CompletedTreatmentAutism, Early Infantile / Schizophrenic Disorders1
1RecruitingTreatmentSchizophrenic Disorders1
2CompletedTreatmentAffective Disorders / Asperger's Syndrome / Autistic Disorder / Bipolar I Disorder / Bipolar II Disorder / Child Development Disorders, Pervasive / Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenic Disorders / Schizophreniform Disorder / Severe Major Depression With Psychotic Features / Severe Mood Disorder With Psychotic Features / Single Episode Major Depression Without Psychotic Symptoms1
2CompletedTreatmentSchizophrenic Disorders4
2RecruitingTreatmentDepression, Bipolar / Suicidal Ideas / Suicidal Ideation / Suicide, Attempted1
2RecruitingTreatmentSchizophrenic Disorders1
2, 3Not Yet RecruitingTreatmentDepression, Bipolar / Suicidal Ideation1
3Active Not RecruitingTreatmentAutism, Early Infantile / Depression, Bipolar / Schizophrenic Disorders1
3Active Not RecruitingTreatmentDepression, Bipolar1
3CompletedTreatmentAutism, Early Infantile1
3CompletedTreatmentBipolar Disorder (BD) / Schizophrenic Disorders1
3CompletedTreatmentBipolar I Disorder4
3CompletedTreatmentDepression, Bipolar5
3CompletedTreatmentMajor Depressive Disorder (MDD)1
3CompletedTreatmentMajor Depressive Disorder With Mixed Features1
3CompletedTreatmentSchizoaffective Disorders / Schizophrenic Disorders1
3CompletedTreatmentSchizophrenic Disorders10
3RecruitingTreatmentBipolar Disorder (BD)1
3WithdrawnTreatmentMajor Depressive Disorder (MDD)1
4CompletedTreatmentPsychotic Disorder NOS1
4CompletedTreatmentSchizoaffective Disorders / Schizophrenic Disorders1
4CompletedTreatmentSchizophrenic Disorders2
4Not Yet RecruitingTreatmentSchizophrenic Disorders1
4RecruitingTreatmentSchizophrenic Disorders1
4WithdrawnTreatmentBipolar Disorder (BD) / Bipolar I / Bipolar II / Bipolar Spectrum Disorder / Mania1
Not AvailableCompletedNot AvailableBipolar Disorder (BD)1
Not AvailableCompletedTreatmentDepression, Bipolar1
Not AvailableEnrolling by InvitationNot AvailableBipolar Disorder (BD)1
Not AvailableRecruitingNot AvailableAcute Bacterial Exacerbation of Chronic Bronchitis (ABECB) / Acute Bacterial Sinusitis (ABS) / Acute Decompensated Heart Failure (ADHF) / Acute Pyelonephritis / Adenovirus / Adjunct to general anesthesia therapy / Adrenal Insufficiency / Airway Swelling / Anaesthesia therapy / Anxiolysis / Arterial Hypotension / Autism, Early Infantile / Autistic Disorder / Bartonellosis / Benzodiazepine Withdrawal / Benzodiazepines / Bipolar Disorder (BD) / Bloodstream Infections / Bone and Joint Infections / Brain Swelling / Bronchospasm / Brucellosis / Cardiac Arrest / Central Nervous System Infections / Cholera / Chronic Bacterial Prostatitis / Community Acquired Pneumonia (CAP) / Complicated Urinary Tract Infections / Convulsions / Cyanide Poisoning / Cytomegalovirus Retinitis / Drug hypersensitivity reaction / Early-onset Schizophrenia Spectrum Disorders / Edema / Epilepsies / Feeling Anxious / Flu caused by Influenza / Gastroparesis / Gynaecological infection / Headaches / Herpes Simplex Virus / High Blood Cholesterol Level / High Blood Pressure (Hypertension) / Hospital-acquired bacterial pneumonia / Hyperlipidemias / Infantile Hemangiomas / Infection NOS / Inflammatory Conditions / Inflammatory Reaction / Influenza Treatment or Prophylaxis / Inhalational Anthrax (Post-Exposure) / Intra-Abdominal Infections / Life-threatening Fungal Infections / Lower Respiratory Tract Infection (LRTI) / Meningitis, Bacterial / Migraines / Muscle Spasms / Nausea / Opioid Addiction / Pain / Plague / Pneumonia / Prophylaxis / Psittacosis / Q Fever / Reflux / Relapsing Fever / Rocky Mountain Spotted Fever / Schizophrenic Disorders / Sedation therapy / Seizures / Sepsis / Skeletal Muscle Spasms / Skin and Subcutaneous Tissue Bacterial Infections / Skin Structures and Soft Tissue Infections / Stable Angina (SA) / Thromboprophylaxis / Thrombosis / Trachoma / Treatment-resistant Schizophrenia / Tularemia / Typhus Fever / Uncomplicated Skin and Skin Structure Infections / Uncomplicated Urinary Tract Infections / Urinary Tract Infections (UTIs) / Vomiting / Withdrawal1
Not AvailableUnknown StatusNot AvailableSchizophrenic Disorders1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral120 mg
TabletOral20 mg
TabletOral40 mg
TabletOral60 mg
TabletOral80 mg
Tablet, film coatedOral120 mg/1
Tablet, film coatedOral20 mg/1
Tablet, film coatedOral40 mg/1
Tablet, film coatedOral60 mg/1
Tablet, film coatedOral80 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US9174975Yes2006-12-252026-12-25Us
US9259423Yes2011-11-232031-11-23Us
US8729085Yes2006-11-262026-11-26Us
US5532372Yes1999-01-022019-01-02Us
US8883794Yes2006-11-262026-11-26Us
USRE45573Yes2005-12-232025-12-23Us
US9555027No2006-05-262026-05-26Us
US9815827No2004-02-202024-02-20Us
US9827242No2011-05-232031-05-23Us
US9907794No2006-05-262026-05-26Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00789 mg/mLALOGPS
logP5.25ALOGPS
logP4.56ChemAxon
logS-4.8ALOGPS
pKa (Strongest Basic)8.5ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area56.75 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity139.33 m3·mol-1ChemAxon
Polarizability56.2 Å3ChemAxon
Number of Rings7ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9907
Caco-2 permeable+0.5257
P-glycoprotein substrateSubstrate0.6029
P-glycoprotein inhibitor IInhibitor0.6713
P-glycoprotein inhibitor IIInhibitor0.73
Renal organic cation transporterInhibitor0.5487
CYP450 2C9 substrateNon-substrate0.7897
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.5922
CYP450 1A2 substrateNon-inhibitor0.677
CYP450 2C9 inhibitorInhibitor0.6714
CYP450 2D6 inhibitorNon-inhibitor0.8292
CYP450 2C19 inhibitorInhibitor0.7439
CYP450 3A4 inhibitorNon-inhibitor0.7835
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8126
Ames testNon AMES toxic0.6477
CarcinogenicityNon-carcinogens0.8986
BiodegradationNot ready biodegradable0.9959
Rat acute toxicity2.4051 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6636
hERG inhibition (predictor II)Inhibitor0.5858
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as n-arylpiperazines. These are organic compounds containing a piperazine ring where the nitrogen ring atom carries an aryl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazinanes
Sub Class
Piperazines
Direct Parent
N-arylpiperazines
Alternative Parents
Aromatic monoterpenoids / Isoindolones / Benzothiazoles / Dialkylarylamines / N-alkylpiperazines / Aminothiazoles / Benzenoids / Pyrrolidine-2-ones / Imidolactams / N-substituted carboxylic acid imides
show 11 more
Substituents
N-arylpiperazine / Aromatic monoterpenoid / Monoterpenoid / Norbornane monoterpenoid / Isoindolone / 1,2-benzothiazole / Isoindoline / Isoindole or derivatives / Dialkylarylamine / N-alkylpiperazine
show 29 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
N-arylpiperazine, dicarboximide, bridged compound, 1,2-benzisothiazole (CHEBI:70735)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
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. George M, Amrutheshwar R, Rajkumar RP, Kattimani S, Dkhar SA: Newer antipsychotics and upcoming molecules for schizophrenia. Eur J Clin Pharmacol. 2013 Aug;69(8):1497-509. doi: 10.1007/s00228-013-1498-4. Epub 2013 Apr 2. [PubMed:23545936]
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. George M, Amrutheshwar R, Rajkumar RP, Kattimani S, Dkhar SA: Newer antipsychotics and upcoming molecules for schizophrenia. Eur J Clin Pharmacol. 2013 Aug;69(8):1497-509. doi: 10.1007/s00228-013-1498-4. Epub 2013 Apr 2. [PubMed:23545936]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
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. George M, Amrutheshwar R, Rajkumar RP, Kattimani S, Dkhar SA: Newer antipsychotics and upcoming molecules for schizophrenia. Eur J Clin Pharmacol. 2013 Aug;69(8):1497-509. doi: 10.1007/s00228-013-1498-4. Epub 2013 Apr 2. [PubMed:23545936]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
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. George M, Amrutheshwar R, Rajkumar RP, Kattimani S, Dkhar SA: Newer antipsychotics and upcoming molecules for schizophrenia. Eur J Clin Pharmacol. 2013 Aug;69(8):1497-509. doi: 10.1007/s00228-013-1498-4. Epub 2013 Apr 2. [PubMed:23545936]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
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. George M, Amrutheshwar R, Rajkumar RP, Kattimani S, Dkhar SA: Newer antipsychotics and upcoming molecules for schizophrenia. Eur J Clin Pharmacol. 2013 Aug;69(8):1497-509. doi: 10.1007/s00228-013-1498-4. Epub 2013 Apr 2. [PubMed:23545936]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
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. Tarazi FI, Stahl SM: Iloperidone, asenapine and lurasidone: a primer on their current status. Expert Opin Pharmacother. 2012 Sep;13(13):1911-22. doi: 10.1517/14656566.2012.712114. Epub 2012 Jul 31. [PubMed:22849428]

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. George M, Amrutheshwar R, Rajkumar RP, Kattimani S, Dkhar SA: Newer antipsychotics and upcoming molecules for schizophrenia. Eur J Clin Pharmacol. 2013 Aug;69(8):1497-509. doi: 10.1007/s00228-013-1498-4. Epub 2013 Apr 2. [PubMed:23545936]
  2. Lurasidone HCl FDA Label [Link]

Drug created on July 24, 2011 11:04 / Updated on September 22, 2018 22:35