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Identification
NameRimonabant
Accession NumberDB06155
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionRimonabant is an anorectic anti-obesity drug produced and marketed by Sanofi-Aventis. It is an inverse agonist for the cannabinoid receptor CB1. Its main avenue of effect is reduction in appetite. Rimonabant is the first selective CB1 receptor blocker to be approved for use anywhere in the world. Rimonabant is approved in 38 countries including the E.U., Mexico, and Brazil. It was rejected for approval for use in the United States. This decision was made after a U.S. advisory panel recommended the medicine not be approved because it may increase suicidal thinking and depression.
Structure
Thumb
SynonymsNot Available
External Identifiers
  • SR141716
  • SR141716A
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AcompliaTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
AcompliaTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
AcompliaTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
AcompliaTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
AcompliaTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
AcompliaTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
AcompliaTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
AcompliaTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
AcompliaTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
AcompliaTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
AcompliaTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
ZimultiTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
ZimultiTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
ZimultiTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
ZimultiTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
ZimultiTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
ZimultiTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
ZimultiTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
ZimultiTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
ZimultiTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
ZimultiTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
ZimultiTablet, film coated20 mgOralSanofi Aventis2006-06-19Not applicableEu
International Brands
NameCompany
AcompliaNot Available
RimoslimNot Available
RiobantNot Available
SlimonaNot Available
ZimultiNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Rimonabant hydrochloride
158681-13-1
Thumb
  • InChI Key: REOYOKXLUFHOBV-UHFFFAOYSA-N
  • Monoisotopic Mass: 498.0547721
  • Average Mass: 500.25
DBSALT001850
Categories
UNIIRML78EN3XE
CAS number168273-06-1
WeightAverage: 463.787
Monoisotopic: 462.078094435
Chemical FormulaC22H21Cl3N4O
InChI KeyJZCPYUJPEARBJL-UHFFFAOYSA-N
InChI
InChI=1S/C22H21Cl3N4O/c1-14-20(22(30)27-28-11-3-2-4-12-28)26-29(19-10-9-17(24)13-18(19)25)21(14)15-5-7-16(23)8-6-15/h5-10,13H,2-4,11-12H2,1H3,(H,27,30)
IUPAC Name
5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide
SMILES
CC1=C(N(N=C1C(=O)NN1CCCCC1)C1=C(Cl)C=C(Cl)C=C1)C1=CC=C(Cl)C=C1
Pharmacology
IndicationFor use in conjunction with diet and exercise for patients with a body mass index greater than 30 kg/m2, or patients wih a BMI greater than 27 kg/m2 with associated risk factors, such as type 2 diabetes or dyslipidaemia.
Structured Indications Not Available
PharmacodynamicsIn the RIO-North America trial, 3040 patients were randomized to receive either placebo or one of two doses of rimonabant (5 mg or 20 mg per day). Patients taking 20 mg rimonabant had significant weigh loss, decrease in waist circumference, improved insulin sensitivity, and increases in HDL cholesterol, compared to patients on placebo.
Mechanism of actionRimonabant is a specific CB1 cannabinoid receptor antagonist. There is considerable evidence that the endocannabinoid (endogenous cannabinoid) system plays a significant role in appetitive drive and associated behaviours. It is therefore reasonable to hypothesize that the attenuation of the activity of this system would have therapeutic benefit in treating disorders that might have a component of excess appetitive drive or over-activity of the endocannabinoid system, such as obesity, ethanol and other drug abuse, and a variety of central nervous system and other disorders.
TargetKindPharmacological actionActionsOrganismUniProt ID
Cannabinoid receptor 1Proteinyes
antagonist
HumanP21554 details
Related Articles
AbsorptionUndetermined
Volume of distributionNot Available
Protein bindingAlmost 100%
Metabolism

Hepatic, CYP3A4 involved.

Route of eliminationNot Available
Half life6 to 9 days with normal BMI and 16 days if BMI is greater than 30
ClearanceNot Available
ToxicityAlmost twice as many people discontinued rimonabant compared with placebo because of adverse events (13.8% vs. 7.2%). These consistently involved psychiatric disorders (8.5% vs. 3.2%), including depression and anxiety. Other common side effects included insomnia, nausea, vomiting, diarrhoea and fatigue.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AmiodaroneThe metabolism of Rimonabant can be decreased when combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Rimonabant can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe metabolism of Rimonabant can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Rimonabant can be decreased when combined with Atomoxetine.Approved
BexaroteneThe serum concentration of Rimonabant can be decreased when it is combined with Bexarotene.Approved, Investigational
BoceprevirThe metabolism of Rimonabant can be decreased when combined with Boceprevir.Approved
BortezomibThe metabolism of Rimonabant can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Rimonabant can be decreased when it is combined with Bosentan.Approved, Investigational
CarbamazepineThe metabolism of Rimonabant can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Rimonabant can be increased when it is combined with Ceritinib.Approved
ClarithromycinThe metabolism of Rimonabant can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Rimonabant can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Rimonabant can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of Rimonabant can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Rimonabant can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Rimonabant can be decreased when combined with Crizotinib.Approved
CyclosporineThe metabolism of Rimonabant can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Rimonabant can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe metabolism of Rimonabant can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Rimonabant can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Rimonabant can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Rimonabant can be decreased when combined with Delavirdine.Approved
DexamethasoneThe serum concentration of Rimonabant can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DihydroergotamineThe metabolism of Rimonabant can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Rimonabant can be decreased when combined with Diltiazem.Approved
DoxycyclineThe metabolism of Rimonabant can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Rimonabant can be decreased when combined with Dronedarone.Approved
EfavirenzThe serum concentration of Rimonabant can be decreased when it is combined with Efavirenz.Approved, Investigational
EnzalutamideThe serum concentration of Rimonabant can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Rimonabant can be decreased when combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe serum concentration of Rimonabant can be decreased when it is combined with Eslicarbazepine acetate.Approved
EtravirineThe serum concentration of Rimonabant can be decreased when it is combined with Etravirine.Approved
FluconazoleThe metabolism of Rimonabant can be decreased when combined with Fluconazole.Approved
FluvoxamineThe metabolism of Rimonabant can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Rimonabant can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Rimonabant can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Rimonabant can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Rimonabant can be increased when it is combined with Fusidic Acid.Approved
IdelalisibThe serum concentration of Rimonabant can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Rimonabant can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Rimonabant can be decreased when combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Rimonabant can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Rimonabant can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Rimonabant can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Rimonabant can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Rimonabant can be decreased when combined with Ketoconazole.Approved, Investigational
LopinavirThe metabolism of Rimonabant can be decreased when combined with Lopinavir.Approved
LovastatinThe metabolism of Rimonabant can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Rimonabant can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Rimonabant can be increased when combined with Lumacaftor.Approved
MifepristoneThe serum concentration of Rimonabant can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Rimonabant can be decreased when it is combined with Mitotane.Approved
ModafinilThe serum concentration of Rimonabant can be decreased when it is combined with Modafinil.Approved, Investigational
NafcillinThe serum concentration of Rimonabant can be decreased when it is combined with Nafcillin.Approved
NefazodoneThe metabolism of Rimonabant can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Rimonabant can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Rimonabant can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Rimonabant can be increased when combined with Nevirapine.Approved
NilotinibThe metabolism of Rimonabant can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Rimonabant can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Rimonabant can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Rimonabant can be increased when it is combined with Palbociclib.Approved
PentobarbitalThe metabolism of Rimonabant can be increased when combined with Pentobarbital.Approved, Vet Approved
PhenobarbitalThe metabolism of Rimonabant can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Rimonabant can be increased when combined with Phenytoin.Approved, Vet Approved
PosaconazoleThe metabolism of Rimonabant can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Rimonabant can be increased when combined with Primidone.Approved, Vet Approved
RanolazineThe metabolism of Rimonabant can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Rimonabant can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Rimonabant can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Rimonabant can be increased when combined with Rifapentine.Approved
RitonavirThe metabolism of Rimonabant can be decreased when combined with Ritonavir.Approved, Investigational
SaquinavirThe metabolism of Rimonabant can be decreased when combined with Saquinavir.Approved, Investigational
SildenafilThe metabolism of Rimonabant can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Rimonabant can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Rimonabant can be increased when it is combined with Simeprevir.Approved
St. John's WortThe serum concentration of Rimonabant can be decreased when it is combined with St. John's Wort.Nutraceutical
StiripentolThe serum concentration of Rimonabant can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Rimonabant can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe metabolism of Rimonabant can be decreased when combined with Telaprevir.Approved
TelithromycinThe metabolism of Rimonabant can be decreased when combined with Telithromycin.Approved
TiclopidineThe metabolism of Rimonabant can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Rimonabant can be decreased when it is combined with Tocilizumab.Approved
VenlafaxineThe metabolism of Rimonabant can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Rimonabant can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Rimonabant can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Rimonabant can be decreased when combined with Ziprasidone.Approved
Food InteractionsNot Available
References
Synthesis Reference

Alain Alcade, Gilles Anne-Archard, Corinne Gavory, Olivier Monnier, “Polymorphic form of rimonabant method for preparing it and pharmaceutical compositions containing it.” U.S. Patent US20050043356, issued February 24, 2005.

US20050043356
General References
  1. Gelfand EV, Cannon CP: Rimonabant: a selective blocker of the cannabinoid CB1 receptors for the management of obesity, smoking cessation and cardiometabolic risk factors. Expert Opin Investig Drugs. 2006 Mar;15(3):307-15. [PubMed:16503766 ]
  2. Xie S, Furjanic MA, Ferrara JJ, McAndrew NR, Ardino EL, Ngondara A, Bernstein Y, Thomas KJ, Kim E, Walker JM, Nagar S, Ward SJ, Raffa RB: The endocannabinoid system and rimonabant: a new drug with a novel mechanism of action involving cannabinoid CB1 receptor antagonism--or inverse agonism--as potential obesity treatment and other therapeutic use. J Clin Pharm Ther. 2007 Jun;32(3):209-31. [PubMed:17489873 ]
  3. Cahill K, Ussher M: Cannabinoid type 1 receptor antagonists (rimonabant) for smoking cessation. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005353. [PubMed:17943852 ]
  4. Maldonado R, Valverde O, Berrendero F: Involvement of the endocannabinoid system in drug addiction. Trends Neurosci. 2006 Apr;29(4):225-32. Epub 2006 Feb 17. [PubMed:16483675 ]
  5. Deadwyler SA, Goonawardena AV, Hampson RE: Short-term memory is modulated by the spontaneous release of endocannabinoids: evidence from hippocampal population codes. Behav Pharmacol. 2007 Sep;18(5-6):571-80. [PubMed:17762525 ]
  6. Huestis MA, Gorelick DA, Heishman SJ, Preston KL, Nelson RA, Moolchan ET, Frank RA: Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716. Arch Gen Psychiatry. 2001 Apr;58(4):322-8. [PubMed:11296091 ]
External Links
ATC CodesA08AX01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (69.1 KB)
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.8799
Caco-2 permeable-0.6262
P-glycoprotein substrateSubstrate0.5723
P-glycoprotein inhibitor IInhibitor0.5864
P-glycoprotein inhibitor IINon-inhibitor0.9065
Renal organic cation transporterNon-inhibitor0.5902
CYP450 2C9 substrateNon-substrate0.6828
CYP450 2D6 substrateNon-substrate0.7198
CYP450 3A4 substrateSubstrate0.734
CYP450 1A2 substrateNon-inhibitor0.6107
CYP450 2C9 inhibitorInhibitor0.8837
CYP450 2D6 inhibitorInhibitor0.8367
CYP450 2C19 inhibitorInhibitor0.885
CYP450 3A4 inhibitorNon-inhibitor0.7535
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9216
Ames testNon AMES toxic0.5896
CarcinogenicityNon-carcinogens0.7543
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5418 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.683
hERG inhibition (predictor II)Inhibitor0.7958
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tablet, film coatedOral20 mg
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.002 mg/mLALOGPS
logP5.47ALOGPS
logP5.91ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)12.42ChemAxon
pKa (Strongest Basic)1.68ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area50.16 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity122.83 m3·mol-1ChemAxon
Polarizability47.96 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylpyrazoles. These are compounds containing a phenylpyrazole skeleton, which consists of a pyrazole bound to a phenyl group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzoles
Sub ClassPyrazoles
Direct ParentPhenylpyrazoles
Alternative Parents
Substituents
  • Phenylpyrazole
  • 1,3-dichlorobenzene
  • Halobenzene
  • Chlorobenzene
  • 1-aminopiperidine
  • Benzenoid
  • Piperidine
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl chloride
  • Heteroaromatic compound
  • Carboxylic acid hydrazide
  • Carboxamide group
  • Azacycle
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Drug binding
Specific Function:
Involved in cannabinoid-induced CNS effects. Acts by inhibiting adenylate cyclase. Could be a receptor for anandamide. Inhibits L-type Ca(2+) channel current. Isoform 2 and isoform 3 have altered ligand binding.
Gene Name:
CNR1
Uniprot ID:
P21554
Molecular Weight:
52857.365 Da
References
  1. Shire D, Calandra B, Delpech M, Dumont X, Kaghad M, Le Fur G, Caput D, Ferrara P: Structural features of the central cannabinoid CB1 receptor involved in the binding of the specific CB1 antagonist SR 141716A. J Biol Chem. 1996 Mar 22;271(12):6941-6. [PubMed:8636122 ]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Leite CE, Mocelin CA, Petersen GO, Leal MB, Thiesen FV: Rimonabant: an antagonist drug of the endocannabinoid system for the treatment of obesity. Pharmacol Rep. 2009 Mar-Apr;61(2):217-24. [PubMed:19443932 ]
  2. Lazary J, Juhasz G, Hunyady L, Bagdy G: Personalized medicine can pave the way for the safe use of CB(1) receptor antagonists. Trends Pharmacol Sci. 2011 May;32(5):270-80. doi: 10.1016/j.tips.2011.02.013. Epub 2011 Apr 16. [PubMed:21497918 ]
Comments
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Drug created on February 14, 2008 10:07 / Updated on August 17, 2016 12:24