Identification

Name
Lorcaserin
Accession Number
DB04871
Type
Small Molecule
Groups
Approved
Description

Lorcaserin (previously APD-356), a highly selective 5HT2C receptor agonist, is used for the treatment of obesity. It has been shown to reduce body weight and food intake in animal models of obesity, and it is thought that targeting the 5HT2C receptor may alter body weight by regulating satiety. Lorcaserin is marketed as a salt form called Belviq, which is lorcaserin hydrochloride.

Structure
Thumb
Synonyms
  • Lorqess
Product Ingredients
IngredientUNIICASInChI Key
Lorcaserin hydrochloride0QJF08GDPE846589-98-8ITIHHRMYZPNGRC-QRPNPIFTSA-N
Lorcaserin hydrochloride hemihydrateREV26SR2B4856681-05-5WRZCAWKMTLRWPR-VSODYHHCSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BelviqTablet10 mg/1OralEisai Limited2012-06-27Not applicableUs
Belviq XRTablet, film coated, extended release20 mg/1OralEisai Limited2016-07-15Not applicableUs
International/Other Brands
Lorqess
Categories
UNII
637E494O0Z
CAS number
616202-92-7
Weight
Average: 195.69
Monoisotopic: 195.0814772
Chemical Formula
C11H14ClN
InChI Key
XTTZERNUQAFMOF-QMMMGPOBSA-N
InChI
InChI=1S/C11H14ClN/c1-8-7-13-5-4-9-2-3-10(12)6-11(8)9/h2-3,6,8,13H,4-5,7H2,1H3/t8-/m0/s1
IUPAC Name
(1R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine
SMILES
C[C@H]1CNCCC2=CC=C(Cl)C=C12

Pharmacology

Indication

For the treatment of obesity, as an adjunct to a reduced-calorie diet and increased physical activity.

Associated Conditions
Pharmacodynamics

Lorcaserin produced a dose-dependent weight loss over a 12-week period by promoting satiety and decreasing food consumption.

Mechanism of action

Although the exact mechanism is unknown, it is believed to involve the selective activation of 5-HT2C receptors in the anorexigenic pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus. This results in decreased food intake and satiety by promoting the release of alpha-melanocortin stimulating hormone, which acts on melanocortin-4 receptors.

TargetActionsOrganism
U5-hydroxytryptamine receptor 2CNot AvailableHuman
Absorption

Lorcaserin has a peak plasma concentration of about 1.5 - 2 hours, but the bioavailability was not determined.

Volume of distribution

The volume of distribution was not determined, but lorcaserin distributes to the central nervous system and cerebrospinal fluid.

Protein binding

Lorcaserin hydrochloride has a plasma protein binding of approximately 70%.

Metabolism

Lorcaserin has extensive hepatic metabolism producing inactive compounds. Lorcaserin sulfamate (M1) is the major metabolite circulating in the plasma, and N-carbamoyl glucuronide lorcaserin (M5) is the major metabolite in urine. Other minor metabolites that are both excreted in urine are glucuronide or sulfate conjugates.

Route of elimination

Lorcaserin is eliminated by hepatic metabolism, and the metabolites are eliminated mostly in the urine (92.3%) and some through feces (2.2%).

Half life

The plasma half life is approximately 11 hours.

Clearance

The clearance value was not determined.

Toxicity

Most common adverse reactions include hypoglycemia (diabetic patients), headache, back pain,fatigue, decrease in lymphocytes,upper respiratory tract infection, and nasopharyngitis. Moreover, the safety and efficacy of coadministration with other weight loss products has not been established, and cardiovascular effects on mortality and morbidity have not been established.

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

Interactions

Drug Interactions
DrugInteraction
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Lorcaserin.
AbirateroneThe serum concentration of Lorcaserin can be increased when it is combined with Abiraterone.
AcebutololThe metabolism of Acebutolol can be decreased when combined with Lorcaserin.
AcepromazineThe risk or severity of adverse effects can be increased when Lorcaserin is combined with Acepromazine.
AceprometazineThe risk or severity of adverse effects can be increased when Lorcaserin is combined with Aceprometazine.
AcetaminophenAcetaminophen may decrease the excretion rate of Lorcaserin which could result in a higher serum level.
AcetophenazineThe risk or severity of adverse effects can be increased when Lorcaserin is combined with Acetophenazine.
Acetyl sulfisoxazoleThe metabolism of Lorcaserin can be decreased when combined with Acetyl sulfisoxazole.
AcetylcholineThe metabolism of Acetylcholine can be decreased when combined with Lorcaserin.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Lorcaserin which could result in a higher serum level.
Food Interactions
  • Administration with or without food has no effect.

References

Synthesis Reference

Jandacek RJ: APD-356 (Arena). Curr Opin Investig Drugs. 2005 Oct;6(10):1051-6.

General References
  1. Halford JC: Obesity drugs in clinical development. Curr Opin Investig Drugs. 2006 Apr;7(4):312-8. [PubMed:16625817]
  2. Smith BM, Smith JM, Tsai JH, Schultz JA, Gilson CA, Estrada SA, Chen RR, Park DM, Prieto EB, Gallardo CS, Sengupta D, Dosa PI, Covel JA, Ren A, Webb RR, Beeley NR, Martin M, Morgan M, Espitia S, Saldana HR, Bjenning C, Whelan KT, Grottick AJ, Menzaghi F, Thomsen WJ: Discovery and structure-activity relationship of (1R)-8-chloro-2,3,4,5-tetrahydro-1-methyl-1H-3-benzazepine (Lorcaserin), a selective serotonin 5-HT2C receptor agonist for the treatment of obesity. J Med Chem. 2008 Jan 24;51(2):305-13. Epub 2007 Dec 21. [PubMed:18095642]
External Links
KEGG Drug
D06613
PubChem Compound
11658860
PubChem Substance
310264855
ChemSpider
9833595
BindingDB
50161646
ChEBI
65353
ChEMBL
CHEMBL360328
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Lorcaserin
ATC Codes
A08AA11 — Lorcaserin
FDA label
Download (401 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingTreatmentCannabis Use Disorders1
1CompletedNot AvailableBMI >30 kg/m22
1CompletedNot AvailableHepatic Impairment1
1CompletedNot AvailableImpaired Renal Function1
1CompletedNot AvailablePharmacokinetics in Obese Adolescents1
1CompletedDiagnosticCocaine Abuse1
1CompletedTreatmentBMI >30 kg/m21
1CompletedTreatmentHealthy Volunteers2
1Enrolling by InvitationPreventionCardiovascular Disease (CVD)1
1Not Yet RecruitingBasic ScienceDependence, Cocaine1
1RecruitingBasic ScienceCocaine Use Disorders1
1RecruitingOtherHealthy Participants1
1RecruitingTreatmentCannabis Use Disorders1
1RecruitingTreatmentCocaine-Related Disorders / Opioid-Related Disorders1
1RecruitingTreatmentOpioid Abuse / Opioid Dependence / Opioid-Related Disorders / Opioids Use1
1, 2CompletedTreatmentTobacco Use Disorders / Weight gain therapy1
1, 2Enrolling by InvitationTreatmentMuscle Weakness / Sepsis1
1, 2RecruitingBasic ScienceCannabis Use1
1, 2RecruitingTreatmentCocaine Use Disorders1
2Active Not RecruitingTreatmentNicotine Dependence1
2CompletedTreatmentBMI >30 kg/m22
2CompletedTreatmentCessation, Smoking1
2RecruitingTreatmentCocaine Use Disorders1
2RecruitingTreatmentCocaine-Related Disorders1
2, 3RecruitingTreatmentBMI >30 kg/m2 / Cessation, Smoking1
2, 3RecruitingTreatmentOpioid-use Disorder1
3CompletedTreatmentBMI >27 kg/m2 / Obese1
3CompletedTreatmentBMI >30 kg/m23
4Active Not RecruitingTreatmentBMI >30 kg/m2 / Obese experiencing rapid weight loss1
4CompletedTreatmentBMI >27 kg/m2 / BMI >30 kg/m2 / Cardiovascular Disease (CVD) / High Cardiovascular Risk / Type 2 Diabetes Mellitus1
4CompletedTreatmentChronic Weight Management1
4RecruitingOtherOverweight and Obesity1
4RecruitingTreatmentBMI >27 kg/m2 / Schizoaffective Disorders / Schizophrenic Disorders1
4RecruitingTreatmentBMI >30 kg/m21
4Unknown StatusTreatmentWeight gain therapy1
Not AvailableActive Not RecruitingNot AvailableBMI >27 kg/m2 / BMI >30 kg/m2 / Obese experiencing rapid weight loss1
Not AvailableCompletedTreatmentBMI >30 kg/m21

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral10 mg/1
Tablet, film coated, extended releaseOral20 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6953787No2003-04-102023-04-10Us
US7514422No2003-04-102023-04-10Us
US7977329No2003-04-102023-04-10Us
US8207158No2003-04-102023-04-10Us
US8273734No2003-04-102023-04-10Us
US8546379No2003-04-102023-04-10Us
US8367657No2003-04-102023-04-10Us
US8575149No2003-04-102023-04-10Us
US9169213No2012-12-062032-12-06Us
US8999970No2013-02-072033-02-07Us
US8980881No2005-12-202025-12-20Us
US8946207No2004-06-162024-06-16Us
US8168624No2009-04-182029-04-18Us
US8697686No2005-12-202025-12-20Us
US7169401No2003-07-182023-07-18Us
US9770455No2011-08-312031-08-31Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityWater solubility is greater than 400 mg/mL.From FDA label.
Predicted Properties
PropertyValueSource
Water Solubility0.0709 mg/mLALOGPS
logP3ALOGPS
logP2.83ChemAxon
logS-3.4ALOGPS
pKa (Strongest Basic)10.12ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area12.03 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity56.65 m3·mol-1ChemAxon
Polarizability21.51 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

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 benzazepines. These are organic compounds containing a benzene ring fused to an azepine ring (unsaturated seven-membered heterocycle with one nitrogen atom replacing a carbon atom).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzazepines
Sub Class
Not Available
Direct Parent
Benzazepines
Alternative Parents
Azepines / Aralkylamines / Benzenoids / Aryl chlorides / Dialkylamines / Azacyclic compounds / Organopnictogen compounds / Organochlorides / Hydrocarbon derivatives
Substituents
Benzazepine / Azepine / Aralkylamine / Benzenoid / Aryl halide / Aryl chloride / Azacycle / Secondary amine / Secondary aliphatic amine / Organonitrogen compound
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organochlorine compound, benzazepine (CHEBI:65353)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
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, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51820.705 Da
References
  1. Halford JC: Obesity drugs in clinical development. Curr Opin Investig Drugs. 2006 Apr;7(4):312-8. [PubMed:16625817]
  2. Jandacek RJ: APD-356 (Arena). Curr Opin Investig Drugs. 2005 Oct;6(10):1051-6. [PubMed:16259227]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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 oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Usmani KA, Chen WG, Sadeque AJ: Identification of human cytochrome P450 and flavin-containing monooxygenase enzymes involved in the metabolism of lorcaserin, a novel selective human 5-hydroxytryptamine 2C agonist. Drug Metab Dispos. 2012 Apr;40(4):761-71. doi: 10.1124/dmd.111.043414. Epub 2012 Jan 20. [PubMed:22266842]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
References
  1. Usmani KA, Chen WG, Sadeque AJ: Identification of human cytochrome P450 and flavin-containing monooxygenase enzymes involved in the metabolism of lorcaserin, a novel selective human 5-hydroxytryptamine 2C agonist. Drug Metab Dispos. 2012 Apr;40(4):761-71. doi: 10.1124/dmd.111.043414. Epub 2012 Jan 20. [PubMed:22266842]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Usmani KA, Chen WG, Sadeque AJ: Identification of human cytochrome P450 and flavin-containing monooxygenase enzymes involved in the metabolism of lorcaserin, a novel selective human 5-hydroxytryptamine 2C agonist. Drug Metab Dispos. 2012 Apr;40(4):761-71. doi: 10.1124/dmd.111.043414. Epub 2012 Jan 20. [PubMed:22266842]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Usmani KA, Chen WG, Sadeque AJ: Identification of human cytochrome P450 and flavin-containing monooxygenase enzymes involved in the metabolism of lorcaserin, a novel selective human 5-hydroxytryptamine 2C agonist. Drug Metab Dispos. 2012 Apr;40(4):761-71. doi: 10.1124/dmd.111.043414. Epub 2012 Jan 20. [PubMed:22266842]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Usmani KA, Chen WG, Sadeque AJ: Identification of human cytochrome P450 and flavin-containing monooxygenase enzymes involved in the metabolism of lorcaserin, a novel selective human 5-hydroxytryptamine 2C agonist. Drug Metab Dispos. 2012 Apr;40(4):761-71. doi: 10.1124/dmd.111.043414. Epub 2012 Jan 20. [PubMed:22266842]
Kind
Protein
Organism
Human
Pharmacological action
No
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. Usmani KA, Chen WG, Sadeque AJ: Identification of human cytochrome P450 and flavin-containing monooxygenase enzymes involved in the metabolism of lorcaserin, a novel selective human 5-hydroxytryptamine 2C agonist. Drug Metab Dispos. 2012 Apr;40(4):761-71. doi: 10.1124/dmd.111.043414. Epub 2012 Jan 20. [PubMed:22266842]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Nadp binding
Specific Function
This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. Form I catalyzes the N-oxygenation of secondary and tertiary amines.
Gene Name
FMO1
Uniprot ID
Q01740
Uniprot Name
Dimethylaniline monooxygenase [N-oxide-forming] 1
Molecular Weight
60310.285 Da
References
  1. Usmani KA, Chen WG, Sadeque AJ: Identification of human cytochrome P450 and flavin-containing monooxygenase enzymes involved in the metabolism of lorcaserin, a novel selective human 5-hydroxytryptamine 2C agonist. Drug Metab Dispos. 2012 Apr;40(4):761-71. doi: 10.1124/dmd.111.043414. Epub 2012 Jan 20. [PubMed:22266842]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d 24-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 oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Usmani KA, Chen WG, Sadeque AJ: Identification of human cytochrome P450 and flavin-containing monooxygenase enzymes involved in the metabolism of lorcaserin, a novel selective human 5-hydroxytryptamine 2C agonist. Drug Metab Dispos. 2012 Apr;40(4):761-71. doi: 10.1124/dmd.111.043414. Epub 2012 Jan 20. [PubMed:22266842]

Drug created on October 20, 2007 04:39 / Updated on September 23, 2018 18:11