You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
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
AcompliaFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
AcompliaFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
AcompliaFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
AcompliaFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
AcompliaFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
AcompliaFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
AcompliaFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
AcompliaFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
AcompliaFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
AcompliaFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
AcompliaFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
ZimultiFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
ZimultiFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
ZimultiFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
ZimultiFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
ZimultiFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
ZimultiFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
ZimultiFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
ZimultiFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
ZimultiFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
ZimultiFilm-coated tablet20 mgOral useSanofi Aventis2006-06-19Not applicableEu
ZimultiFilm-coated tablet20 mgOral useSanofi 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 KeyInChIKey=JZCPYUJPEARBJL-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
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
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.
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.
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
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
Film-coated tabletOral use20 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
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)
Interactions
Drug Interactions
Drug
AmiodaroneThe metabolism of Rimonabant can be decreased when combined with Amiodarone.
AprepitantThe serum concentration of Rimonabant can be increased when it is combined with Aprepitant.
AtazanavirThe metabolism of Rimonabant can be decreased when combined with Atazanavir.
AtomoxetineThe metabolism of Rimonabant can be decreased when combined with Atomoxetine.
BexaroteneThe serum concentration of Rimonabant can be decreased when it is combined with Bexarotene.
BoceprevirThe metabolism of Rimonabant can be decreased when combined with Boceprevir.
BortezomibThe metabolism of Rimonabant can be decreased when combined with Bortezomib.
BosentanThe serum concentration of Rimonabant can be decreased when it is combined with Bosentan.
CarbamazepineThe metabolism of Rimonabant can be increased when combined with Carbamazepine.
CeritinibThe serum concentration of Rimonabant can be increased when it is combined with Ceritinib.
ClarithromycinThe metabolism of Rimonabant can be decreased when combined with Clarithromycin.
ClemastineThe metabolism of Rimonabant can be decreased when combined with Clemastine.
ClotrimazoleThe metabolism of Rimonabant can be decreased when combined with Clotrimazole.
CobicistatThe metabolism of Rimonabant can be decreased when combined with Cobicistat.
ConivaptanThe serum concentration of Rimonabant can be increased when it is combined with Conivaptan.
CrizotinibThe metabolism of Rimonabant can be decreased when combined with Crizotinib.
CyclosporineThe metabolism of Rimonabant can be decreased when combined with Cyclosporine.
DabrafenibThe serum concentration of Rimonabant can be decreased when it is combined with Dabrafenib.
DarunavirThe metabolism of Rimonabant can be decreased when combined with Darunavir.
DasatinibThe serum concentration of Rimonabant can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Rimonabant can be decreased when it is combined with Deferasirox.
DelavirdineThe metabolism of Rimonabant can be decreased when combined with Delavirdine.
DexamethasoneThe serum concentration of Rimonabant can be decreased when it is combined with Dexamethasone.
DihydroergotamineThe metabolism of Rimonabant can be decreased when combined with Dihydroergotamine.
DiltiazemThe metabolism of Rimonabant can be decreased when combined with Diltiazem.
DoxycyclineThe metabolism of Rimonabant can be decreased when combined with Doxycycline.
DronedaroneThe metabolism of Rimonabant can be decreased when combined with Dronedarone.
EfavirenzThe serum concentration of Rimonabant can be decreased when it is combined with Efavirenz.
EnzalutamideThe serum concentration of Rimonabant can be decreased when it is combined with Enzalutamide.
ErythromycinThe metabolism of Rimonabant can be decreased when combined with Erythromycin.
Eslicarbazepine acetateThe serum concentration of Rimonabant can be decreased when it is combined with Eslicarbazepine acetate.
EtravirineThe serum concentration of Rimonabant can be decreased when it is combined with Etravirine.
FluconazoleThe metabolism of Rimonabant can be decreased when combined with Fluconazole.
FluvoxamineThe metabolism of Rimonabant can be decreased when combined with Fluvoxamine.
FosamprenavirThe metabolism of Rimonabant can be decreased when combined with Fosamprenavir.
FosaprepitantThe serum concentration of Rimonabant can be increased when it is combined with Fosaprepitant.
FosphenytoinThe metabolism of Rimonabant can be increased when combined with Fosphenytoin.
Fusidic AcidThe serum concentration of Rimonabant can be increased when it is combined with Fusidic Acid.
IdelalisibThe serum concentration of Rimonabant can be increased when it is combined with Idelalisib.
ImatinibThe metabolism of Rimonabant can be decreased when combined with Imatinib.
IndinavirThe metabolism of Rimonabant can be decreased when combined with Indinavir.
IsavuconazoniumThe metabolism of Rimonabant can be decreased when combined with Isavuconazonium.
IsradipineThe metabolism of Rimonabant can be decreased when combined with Isradipine.
ItraconazoleThe metabolism of Rimonabant can be decreased when combined with Itraconazole.
IvacaftorThe serum concentration of Rimonabant can be increased when it is combined with Ivacaftor.
KetoconazoleThe metabolism of Rimonabant can be decreased when combined with Ketoconazole.
LopinavirThe metabolism of Rimonabant can be decreased when combined with Lopinavir.
LovastatinThe metabolism of Rimonabant can be decreased when combined with Lovastatin.
LuliconazoleThe serum concentration of Rimonabant can be increased when it is combined with Luliconazole.
MifepristoneThe metabolism of Rimonabant can be decreased when combined with Mifepristone.
MitotaneThe serum concentration of Rimonabant can be decreased when it is combined with Mitotane.
ModafinilThe serum concentration of Rimonabant can be decreased when it is combined with Modafinil.
NafcillinThe serum concentration of Rimonabant can be decreased when it is combined with Nafcillin.
NefazodoneThe metabolism of Rimonabant can be decreased when combined with Nefazodone.
NelfinavirThe metabolism of Rimonabant can be decreased when combined with Nelfinavir.
NetupitantThe serum concentration of Rimonabant can be increased when it is combined with Netupitant.
NevirapineThe metabolism of Rimonabant can be decreased when combined with Nevirapine.
NilotinibThe metabolism of Rimonabant can be decreased when combined with Nilotinib.
OlaparibThe metabolism of Rimonabant can be decreased when combined with Olaparib.
OsimertinibThe serum concentration of Rimonabant can be increased when it is combined with Osimertinib.
PalbociclibThe serum concentration of Rimonabant can be increased when it is combined with Palbociclib.
PentobarbitalThe metabolism of Rimonabant can be increased when combined with Pentobarbital.
PhenobarbitalThe metabolism of Rimonabant can be increased when combined with Phenobarbital.
PhenytoinThe metabolism of Rimonabant can be increased when combined with Phenytoin.
PosaconazoleThe metabolism of Rimonabant can be decreased when combined with Posaconazole.
PrimidoneThe metabolism of Rimonabant can be increased when combined with Primidone.
RanolazineThe metabolism of Rimonabant can be decreased when combined with Ranolazine.
RifabutinThe metabolism of Rimonabant can be increased when combined with Rifabutin.
RifampicinThe metabolism of Rimonabant can be increased when combined with Rifampicin.
RifapentineThe metabolism of Rimonabant can be increased when combined with Rifapentine.
RitonavirThe metabolism of Rimonabant can be decreased when combined with Ritonavir.
SaquinavirThe metabolism of Rimonabant can be decreased when combined with Saquinavir.
SildenafilThe metabolism of Rimonabant can be decreased when combined with Sildenafil.
SiltuximabThe serum concentration of Rimonabant can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Rimonabant can be increased when it is combined with Simeprevir.
St. John's WortThe serum concentration of Rimonabant can be decreased when it is combined with St. John's Wort.
StiripentolThe serum concentration of Rimonabant can be increased when it is combined with Stiripentol.
SulfisoxazoleThe metabolism of Rimonabant can be decreased when combined with Sulfisoxazole.
TelaprevirThe metabolism of Rimonabant can be decreased when combined with Telaprevir.
TelithromycinThe metabolism of Rimonabant can be decreased when combined with Telithromycin.
TiclopidineThe metabolism of Rimonabant can be decreased when combined with Ticlopidine.
TocilizumabThe serum concentration of Rimonabant can be decreased when it is combined with Tocilizumab.
VenlafaxineThe metabolism of Rimonabant can be decreased when combined with Venlafaxine.
VerapamilThe metabolism of Rimonabant can be decreased when combined with Verapamil.
VoriconazoleThe metabolism of Rimonabant can be decreased when combined with Voriconazole.
ZiprasidoneThe metabolism of Rimonabant can be decreased when combined with Ziprasidone.
Food InteractionsNot 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
comments powered by Disqus
Drug created on February 14, 2008 10:07 / Updated on August 17, 2016 12:24