Identification
- Generic Name
- Rimonabant
- DrugBank Accession Number
- DB06155
- Background
Rimonabant 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.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Rimonabant (DB06155)
- Weight
- Average: 463.787
Monoisotopic: 462.078094435 - Chemical Formula
- C22H21Cl3N4O
- Synonyms
- Rimonabant
- External IDs
- A 281
- SR 141716
- SR141716
- SR141716A
Pharmacology
- Indication
For 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.
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
In 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 action
Rimonabant 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.
Target Actions Organism ACannabinoid receptor 1 antagonistHumans UG-protein coupled receptor 55 Not Available Humans - Absorption
Undetermined
- Volume of distribution
Not Available
- Protein binding
Almost 100%
- Metabolism
Hepatic, CYP3A4 involved.
- Route of elimination
Not Available
- Half-life
6 to 9 days with normal BMI and 16 days if BMI is greater than 30
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Almost 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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of adverse effects can be increased when Rimonabant is combined with 1,2-Benzodiazepine. Abametapir The serum concentration of Rimonabant can be increased when it is combined with Abametapir. Acebutolol The risk or severity of Tachycardia can be increased when Rimonabant is combined with Acebutolol. Acetazolamide The risk or severity of adverse effects can be increased when Rimonabant is combined with Acetazolamide. Acetophenazine The risk or severity of adverse effects can be increased when Rimonabant is combined with Acetophenazine. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Rimonabant hydrochloride HL0V2LQZ09 158681-13-1 REOYOKXLUFHOBV-UHFFFAOYSA-N - International/Other Brands
- Rimoslim / Riobant (SUN) / Slimona
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Acomplia Tablet, film coated 20 mg Oral Sanofi Aventis 2016-09-07 2009-01-30 EU 
Acomplia Tablet, film coated 20 mg Oral Sanofi Aventis 2016-09-07 2009-01-30 EU Acomplia Tablet, film coated 20 mg Oral Sanofi Aventis 2016-09-07 2009-01-30 EU Acomplia Tablet, film coated 20 mg Oral Sanofi Aventis 2016-09-07 2009-01-30 EU Acomplia Tablet, film coated 20 mg Oral Sanofi Aventis 2016-09-07 2009-01-30 EU
Categories
- ATC Codes
- A08AX01 — Rimonabant
- Drug Categories
- Agents producing tachycardia
- Alimentary Tract and Metabolism
- Anti-Obesity Agents
- Antiobesity Preparations, Excl. Diet Products
- Cannabinoid Receptor Antagonists
- Cannabinoids and similars
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Neurotransmitter Agents
- Piperidines
- Pyrazoles
- Receptor, Cannabinoid, CB1, antagonists & inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This 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.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Azoles
- Sub Class
- Pyrazoles
- Direct Parent
- Phenylpyrazoles
- Alternative Parents
- Dichlorobenzenes / Piperidines / Aryl chlorides / Heteroaromatic compounds / Hydrazones / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organochlorides / Hydrocarbon derivatives
- Substituents
- 1,3-dichlorobenzene / Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Chlorobenzene / Halobenzene / Heteroaromatic compound / Hydrazone
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- pyrazoles, ring assembly (CHEBI:34967)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- RML78EN3XE
- CAS number
- 168273-06-1
- InChI Key
- 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
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
- 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. [Article]
- 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. [Article]
- Cahill K, Ussher M: Cannabinoid type 1 receptor antagonists (rimonabant) for smoking cessation. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005353. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- External Links
- Human Metabolome Database
- HMDB0015623
- KEGG Drug
- D05731
- KEGG Compound
- C14319
- PubChem Compound
- 104850
- PubChem Substance
- 99443236
- ChemSpider
- 94641
- BindingDB
- 21278
- ChEBI
- 34967
- ChEMBL
- CHEMBL111
- ZINC
- ZINC000001540228
- Therapeutic Targets Database
- DNC001371
- PharmGKB
- PA152407999
- Guide to Pharmacology
- GtP Drug Page
- PDBe Ligand
- AY6
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Rimonabant
- PDB Entries
- 6aji
- MSDS
- Download (69.1 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Terminated Basic Science Obesity 1 4 Unknown Status Prevention Atherosclerosis / Cardiovascular Disease (CVD) 1 3 Completed Prevention Obesity / Weight Loss 1 3 Completed Treatment Coronary Artery Atherosclerosis 1 3 Completed Treatment Diabetes Mellitus, Noninsulin Dependent / Obesity / Obesity in Diabetes 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral Tablet, film coated Oral 20 mg Tablet, coated Oral 20 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.002 mg/mL ALOGPS logP 5.47 ALOGPS logP 5.91 Chemaxon logS -5.4 ALOGPS pKa (Strongest Acidic) 10.8 Chemaxon pKa (Strongest Basic) 1.68 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 50.16 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 122.83 m3·mol-1 Chemaxon Polarizability 47.96 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.8799 Caco-2 permeable - 0.6262 P-glycoprotein substrate Substrate 0.5723 P-glycoprotein inhibitor I Inhibitor 0.5864 P-glycoprotein inhibitor II Non-inhibitor 0.9065 Renal organic cation transporter Non-inhibitor 0.5902 CYP450 2C9 substrate Non-substrate 0.6828 CYP450 2D6 substrate Non-substrate 0.7198 CYP450 3A4 substrate Substrate 0.734 CYP450 1A2 substrate Non-inhibitor 0.6107 CYP450 2C9 inhibitor Inhibitor 0.8837 CYP450 2D6 inhibitor Inhibitor 0.8367 CYP450 2C19 inhibitor Inhibitor 0.885 CYP450 3A4 inhibitor Non-inhibitor 0.7535 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.9216 Ames test Non AMES toxic 0.5896 Carcinogenicity Non-carcinogens 0.7543 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.5418 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.683 hERG inhibition (predictor II) Inhibitor 0.7958
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 204.1941651 predictedDarkChem Lite v0.1.0 [M-H]- 200.19846 predictedDeepCCS 1.0 (2019) [M+H]+ 203.8338651 predictedDarkChem Lite v0.1.0 [M+H]+ 202.55644 predictedDeepCCS 1.0 (2019) [M+Na]+ 204.4799651 predictedDarkChem Lite v0.1.0 [M+Na]+ 209.23454 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- 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 l...
- Gene Name
- CNR1
- Uniprot ID
- P21554
- Uniprot Name
- Cannabinoid receptor 1
- Molecular Weight
- 52857.365 Da
References
- 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. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- G-protein coupled receptor activity
- Specific Function
- May be involved in hyperalgesia associated with inflammatory and neuropathic pain (By similarity). Receptor for L-alpha-lysophosphatidylinositol (LPI). LPI induces Ca(2+) release from intracellular...
- Gene Name
- GPR55
- Uniprot ID
- Q9Y2T6
- Uniprot Name
- G-protein coupled receptor 55
- Molecular Weight
- 36637.12 Da
References
- Kapur A, Zhao P, Sharir H, Bai Y, Caron MG, Barak LS, Abood ME: Atypical responsiveness of the orphan receptor GPR55 to cannabinoid ligands. J Biol Chem. 2009 Oct 23;284(43):29817-27. doi: 10.1074/jbc.M109.050187. Epub 2009 Sep 1. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- 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
- 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. [Article]
- 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. [Article]
Drug created at February 14, 2008 17:07 / Updated at February 21, 2021 18:52