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Sibutramine

July 24, 2017
Common Name

Sibutramine Description

Sibutramine (trade name Meridia in the USA, Reductil in Europe and other countries), usually as sibutramide hydrochloride monohydrate, is an orally administered agent for the treatment of obesity. It is a centrally acting stimliant chemically related to amphetamines. Sibutramine is classified as a Schedlie IV controlled substance in the United States. In October 2010, Sibutramine was withdrawn from Canadian and U.S. markets due to concerns that the drug increases the risk of heart attack and stroke in patients with a history of heart disease. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source ButraminKegg MeridiaMeSH DidesmethylsibutramineMeSH Sibutramine hydrochlorideMeSH Di-desmethylsibutramineMeSH mono-DesmethylsibutramineMeSH (R)-DDMSMeSH N-1-(1-(4-Chlorophenyl)cyclobutyl)-3-methylbutyl-N,N-dimethylamine HCLMeSH ReductilMeSH

Chemical Formlia

C17H26ClN Average Molecliar Weight

279.848 Monoisotopic Molecliar Weight

279.175377544 IUPAC Name

{1-[1-(4-chlorophenyl)cyclobutyl]-3-methylbutyl}dimethylamine Traditional Name

sibutramine CAS Registry Number

106650-56-0 SMILES

CC(C)CC(N(C)C)C1(CCC1)C1=CC=C(Cl)C=C1

InChI Identifier

InChI=1S/C17H26ClN/c1-13(2)12-16(19(3)4)17(10-5-11-17)14-6-8-15(18)9-7-14/h6-9,13,16H,5,10-12H2,1-4H3

InChI Key

UNAANXDKBXWMLN-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as chlorobenzenes. These are compounds containing one or more chlorine atoms attached to a benzene moiety. Kingdom

Chemical entities Super Class

Organic compounds Class

Benzenoids Sub Class

Benzene and substituted derivatives Direct Parent

Chlorobenzenes Alternative Parents

  • Aralkylamines
  • Aryl chlorides
  • Trialkylamines
  • Organopnictogen compounds
  • Organochlorides
  • Hydrocarbon derivatives

    • Substituents

  • Aralkylamine
  • Chlorobenzene
  • Aryl halide
  • Aryl chloride
  • Tertiary aliphatic amine
  • Tertiary amine
  • Organic nitrogen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Amine
  • Aromatic homomonocyclic compound

    • Molecliar Framework

    Aromatic homomonocyclic compounds External Descriptors

  • tertiary amino compound (CHEBI:9137 )
  • organochlorine compound (CHEBI:9137 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anorexigenic Agents
  • Antidepressants
  • Antidepressive Agents
  • Appetite Depressants
  • Stimliants

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point191 – 192 °CNot Available Boiling PointNot AvailableNot Available Water Solubility9.40e-04 g/LNot Available LogP5.2Not Available

    Predicted Properties

    Property Value Source Water Solubility0.00094 mg/mLALOGPS logP5.05ALOGPS logP5.2ChemAxon logS-5.5ALOGPS pKa (Strongest Basic)9.77ChemAxon Physiological Charge1ChemAxon Hydrogen Acceptor Count1ChemAxon Hydrogen Donor Count0ChemAxon Polar Surface Area3.24 Å2ChemAxon Rotatable Bond Count5ChemAxon Refractivity83.92 m3·mol-1ChemAxon Polarizability32.9 Å3ChemAxon Number of Rings2ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – , positivesplash10-003r-1930000000-b90a7add9041c09efb5eView in MoNA LC-MS/MS

    LC-MS/MS Spectrum – , positivesplash10-005i-1930000000-524395362f2824760185View in MoNA Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01105

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01105

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Predicted Concentrations

    Biofluid Value Original age Original sex Original condition Comments Blood0-4 uMAdlit (>18 years old)BothNormalPredicted based on drug qualities Blood0-2 umol/mmol creatinineAdlit (>18 years old)BothNormalPredicted based on drug qualities

    Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01105 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    5021 KEGG Compound ID

    C07247 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Sibutramine NuGOwiki Link

    HMDB15237 Metagene Link

    HMDB15237 METLIN ID

    Not Available PubChem Compound

    5210 PDB ID

    Not Available ChEBI ID

    458192

    Product: Formononetin

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Sharma B, Henderson DC: Sibutramine: current status as an anti-obesity drug and its future perspectives. Expert Opin Pharmacother. 2008 Aug;9(12):2161-73. doi: 10.1517/14656566.9.12.2161 . [PubMed:18671470 ]
    2. Tziomalos K, Krassas GE, Tzotzas T: The use of sibutramine in the management of obesity and related disorders: an update. Vasc Health Risk Manag. 2009;5(1):441-52. [PubMed:19475780 ]
    3. Stock MJ: Sibutramine: a review of the pharmacology of a novel anti-obesity agent. Int J Obes Relat Metab Disord. 1997 Mar;21 Suppl 1:S25-9. [PubMed:9130038 ]
    4. Heal DJ, Aspley S, Prow MR, Jackson HC, Martin KF, Cheetham SC: Sibutramine: a novel anti-obesity drug. A review of the pharmacological evidence to differentiate it from d-amphetamine and d-fenfluramine. Int J Obes Relat Metab Disord. 1998 Aug;22 Suppl 1:S18-28; discussion S29. [PubMed:9758240 ]

    Enzymes

    General function:
    Involved in monooxygenase 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 xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
    Gene Name:
    CYP3A4
    Uniprot ID:
    P08684
    Molecular weight:
    57255.585
    References
    1. Sharma B, Henderson DC: Sibutramine: current status as an anti-obesity drug and its future perspectives. Expert Opin Pharmacother. 2008 Aug;9(12):2161-73. doi: 10.1517/14656566.9.12.2161 . [PubMed:18671470 ]
    2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
    General function:
    Involved in neurotransmitter:sodium symporter activity
    Specific function:
    Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
    Gene Name:
    SLC6A3
    Uniprot ID:
    Q01959
    Molecular weight:
    68494.255
    References
    1. Tziomalos K, Krassas GE, Tzotzas T: The use of sibutramine in the management of obesity and related disorders: an update. Vasc Health Risk Manag. 2009;5(1):441-52. [PubMed:19475780 ]
    2. Gomis Barbara R: [Pharmacological treatment of obesity]. Rev Med Univ Navarra. 2004 Apr-Jun;48(2):63-5. [PubMed:15382615 ]
    3. Berke EM, Morden NE: Medical management of obesity. Am Fam Physician. 2000 Jul 15;62(2):419-26. [PubMed:10929704 ]
    4. Nakagawa T, Ukai K, Ohyama T, Gomita Y, Okamura H: Effects of sibutramine on the central dopaminergic system in rodents. Neurotox Res. 2001 Jul;3(3):235-47. [PubMed:15111248 ]
    5. Krahn LE, Moore WR, Altchuler SI: Narcolepsy and obesity: remission of severe cataplexy with sibutramine. Sleep Med. 2001 Jan;2(1):63-65. [PubMed:11152984 ]
    6. Balcioglu A, Wurtman RJ: Sibutramine, a serotonin uptake inhibitor, increases dopamine concentrations in rat striatal and hypothalamic extracellular fluid. Neuropharmacology. 2000 Sep;39(12):2352-9. [PubMed:10974319 ]

    Transporters

    General function:
    Involved in neurotransmitter:sodium symporter activity
    Specific function:
    Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
    Gene Name:
    SLC6A2
    Uniprot ID:
    P23975
    Molecular weight:
    69331.42
    References
    1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    2. Heusser K, Engeli S, Tank J, Diedrich A, Wiesner S, Janke J, Luft FC, Jordan J: Sympathetic vasomotor tone determines blood pressure response to long-term sibutramine treatment. J Clin Endocrinol Metab. 2007 Apr;92(4):1560-3. Epub 2007 Feb 6. [PubMed:17284621 ]
    3. Jordan J, Scholze J, Matiba B, Wirth A, Hauner H, Sharma AM: Influence of Sibutramine on blood pressure: evidence from placebo-controlled trials. Int J Obes (Lond). 2005 May;29(5):509-16. [PubMed:15685250 ]
    4. Heusser K, Tank J, Diedrich A, Engeli S, Klaua S, Kruger N, Strauss A, Stoffels G, Luft FC, Jordan J: Influence of sibutramine treatment on sympathetic vasomotor tone in obese subjects. Clin Pharmacol Ther. 2006 May;79(5):500-8. [PubMed:16678551 ]
    5. Birkenfeld AL, Schroeder C, Boschmann M, Tank J, Franke G, Luft FC, Biaggioni I, Sharma AM, Jordan J: Paradoxical effect of sibutramine on autonomic cardiovascular regulation. Circulation. 2002 Nov 5;106(19):2459-65. [PubMed:12417543 ]
    6. Birkenfeld AL, Schroeder C, Pischon T, Tank J, Luft FC, Sharma AM, Jordan J: Paradoxical effect of sibutramine on autonomic cardiovascular regulation in obese hypertensive patients–sibutramine and blood pressure. Clin Auton Res. 2005 Jun;15(3):200-6. [PubMed:15944869 ]
    7. Tziomalos K, Krassas GE, Tzotzas T: The use of sibutramine in the management of obesity and related disorders: an update. Vasc Health Risk Manag. 2009;5(1):441-52. [PubMed:19475780 ]
    8. Sharma B, Henderson DC: Sibutramine: current status as an anti-obesity drug and its future perspectives. Expert Opin Pharmacother. 2008 Aug;9(12):2161-73. doi: 10.1517/14656566.9.12.2161 . [PubMed:18671470 ]
    9. Gomis Barbara R: [Pharmacological treatment of obesity]. Rev Med Univ Navarra. 2004 Apr-Jun;48(2):63-5. [PubMed:15382615 ]
    10. Berke EM, Morden NE: Medical management of obesity. Am Fam Physician. 2000 Jul 15;62(2):419-26. [PubMed:10929704 ]
    11. Krahn LE, Moore WR, Altchuler SI: Narcolepsy and obesity: remission of severe cataplexy with sibutramine. Sleep Med. 2001 Jan;2(1):63-65. [PubMed:11152984 ]
    General function:
    Involved in neurotransmitter:sodium symporter activity
    Specific function:
    Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
    Gene Name:
    SLC6A4
    Uniprot ID:
    P31645
    Molecular weight:
    70324.165
    References
    1. Vazquez Roque MI, Camilleri M, Clark MM, Tepoel DA, Jensen MD, Graszer KM, Kalsy SA, Burton DD, Baxter KL, Zinsmeister AR: Alteration of gastric functions and candidate genes associated with weight reduction in response to sibutramine. Clin Gastroenterol Hepatol. 2007 Jul;5(7):829-37. Epub 2007 Jun 4. [PubMed:17544870 ]
    2. Heusser K, Engeli S, Tank J, Diedrich A, Wiesner S, Janke J, Luft FC, Jordan J: Sympathetic vasomotor tone determines blood pressure response to long-term sibutramine treatment. J Clin Endocrinol Metab. 2007 Apr;92(4):1560-3. Epub 2007 Feb 6. [PubMed:17284621 ]
    3. Jordan J, Scholze J, Matiba B, Wirth A, Hauner H, Sharma AM: Influence of Sibutramine on blood pressure: evidence from placebo-controlled trials. Int J Obes (Lond). 2005 May;29(5):509-16. [PubMed:15685250 ]
    4. Heusser K, Tank J, Diedrich A, Engeli S, Klaua S, Kruger N, Strauss A, Stoffels G, Luft FC, Jordan J: Influence of sibutramine treatment on sympathetic vasomotor tone in obese subjects. Clin Pharmacol Ther. 2006 May;79(5):500-8. [PubMed:16678551 ]
    5. Birkenfeld AL, Schroeder C, Boschmann M, Tank J, Franke G, Luft FC, Biaggioni I, Sharma AM, Jordan J: Paradoxical effect of sibutramine on autonomic cardiovascular regulation. Circulation. 2002 Nov 5;106(19):2459-65. [PubMed:12417543 ]
    6. Birkenfeld AL, Schroeder C, Pischon T, Tank J, Luft FC, Sharma AM, Jordan J: Paradoxical effect of sibutramine on autonomic cardiovascular regulation in obese hypertensive patients–sibutramine and blood pressure. Clin Auton Res. 2005 Jun;15(3):200-6. [PubMed:15944869 ]
    7. Tziomalos K, Krassas GE, Tzotzas T: The use of sibutramine in the management of obesity and related disorders: an update. Vasc Health Risk Manag. 2009;5(1):441-52. [PubMed:19475780 ]
    8. Sharma B, Henderson DC: Sibutramine: current status as an anti-obesity drug and its future perspectives. Expert Opin Pharmacother. 2008 Aug;9(12):2161-73. doi: 10.1517/14656566.9.12.2161 . [PubMed:18671470 ]
    9. Gomis Barbara R: [Pharmacological treatment of obesity]. Rev Med Univ Navarra. 2004 Apr-Jun;48(2):63-5. [PubMed:15382615 ]
    10. Berke EM, Morden NE: Medical management of obesity. Am Fam Physician. 2000 Jul 15;62(2):419-26. [PubMed:10929704 ]
    11. Krahn LE, Moore WR, Altchuler SI: Narcolepsy and obesity: remission of severe cataplexy with sibutramine. Sleep Med. 2001 Jan;2(1):63-65. [PubMed:11152984 ]

    PMID: 8700839

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