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Record Information
Version3.6
Creation Date2012-09-06 15:16:49 UTC
Update Date2016-02-11 01:28:22 UTC
HMDB IDHMDB14390
Secondary Accession NumbersNone
Metabolite Identification
Common NameBenzatropine
DescriptionBenzotropine is a centrally-acting, antimuscarinic agent used as an adjunct in the treatment of Parkinson's disease. It may also be used to treat extrapyramidal reactions, such as dystonia and Parkinsonism, caused by antipsychotics (e.g. phenothiazines). Symptoms of Parkinson's disease and extrapyramidal reactions arise from decreases in dopaminergic activity which creates an imbalance between dopaminergic and cholinergic activity. Anticholinergic therapy is thought to aid in restoring this balance leading to relief of symptoms. In addition to its anticholinergic effects, benztropine also inhibits the reuptake of dopamine at nerve terminals via the dopamine transporter. Benzotropine also produces antagonistic effects at the histamine H1 receptor.
Structure
Thumb
Synonyms
ValueSource
3alpha-(Diphenylmethoxy)-1alphah,5alphah-tropaneChEBI
3alpha-(Diphenylmethoxy)tropaneChEBI
3alpha-Benzhydryloxy-8-methyl-8-azabicyclo[3.2.1]octaneChEBI
3Endo-BenzhydryloxytropaneChEBI
BenzatropinaChEBI
BenzatropinumChEBI
Benzhydryl 8-methyl-8-azabicyclo[3.2.1]oct-3-yl etherChEBI
BenztropineChEBI
Tropine benzohydryl etherChEBI
3a-(Diphenylmethoxy)-1alphah,5alphah-tropaneGenerator
3α-(diphenylmethoxy)-1alphah,5alphah-tropaneGenerator
3a-(Diphenylmethoxy)tropaneGenerator
3α-(diphenylmethoxy)tropaneGenerator
3a-Benzhydryloxy-8-methyl-8-azabicyclo[3.2.1]octaneGenerator
3α-benzhydryloxy-8-methyl-8-azabicyclo[3.2.1]octaneGenerator
Benzatropine mesilateHMDB
BenztropinumHMDB
Chemical FormulaC21H25NO
Average Molecular Weight307.4293
Monoisotopic Molecular Weight307.193614427
IUPAC Name(1R,3R,5S)-3-(diphenylmethoxy)-8-methyl-8-azabicyclo[3.2.1]octane
Traditional Namebenzatropina
CAS Registry Number86-13-5
SMILES
[H][C@]12CC[C@]([H])(C[C@@]([H])(C1)OC(C1=CC=CC=C1)C1=CC=CC=C1)N2C
InChI Identifier
InChI=1S/C21H25NO/c1-22-18-12-13-19(22)15-20(14-18)23-21(16-8-4-2-5-9-16)17-10-6-3-7-11-17/h2-11,18-21H,12-15H2,1H3/t18-,19+,20+
InChI KeyInChIKey=GIJXKZJWITVLHI-PMOLBWCYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassDiphenylmethanes
Direct ParentDiphenylmethanes
Alternative Parents
Substituents
  • Diphenylmethane
  • Tropane alkaloid
  • Benzylether
  • N-alkylpyrrolidine
  • Piperidine
  • Pyrrolidine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Organoheterocyclic compound
  • Ether
  • Dialkyl ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Antidyskinetics
  • Antiparkinson Agents
  • Muscarinic Antagonists
  • Parasympatholytics
Application
  • Pharmaceutical
Cellular locations
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility1.21e-03 g/LNot Available
LogP4.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0012 mg/mLALOGPS
logP4.47ALOGPS
logP4.19ChemAxon
logS-5.4ALOGPS
pKa (Strongest Basic)9.54ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.47 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity94.24 m3·mol-1ChemAxon
Polarizability35.42 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00245
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00245
  • Not Applicable
details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-3 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-2 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00245
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID16736541
KEGG Compound IDC06846
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkBenztropine
NuGOwiki LinkHMDB14390
Metagene LinkHMDB14390
METLIN IDNot Available
PubChem CompoundNot Available
PDB IDNot Available
ChEBI ID3048
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. van Harten PN, Hoek HW, Matroos GE, Koeter M, Kahn RS: Intermittent neuroleptic treatment and risk for tardive dyskinesia: Curacao Extrapyramidal Syndromes Study III. Am J Psychiatry. 1998 Apr;155(4):565-7. [9546009 ]
  2. Wszola BA, Newell KM, Sprague RL: Risk factors for tardive dyskinesia in a large population of youths and adults. Exp Clin Psychopharmacol. 2001 Aug;9(3):285-96. [11534539 ]

Enzymes

General function:
Involved in monooxygenase 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 imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular weight:
55944.565
References
  1. 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. Epub 2009 Nov 24. [19934256 ]
General function:
Involved in monooxygenase 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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
References
  1. 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. Epub 2009 Nov 24. [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. Katz JL, Agoston GE, Alling KL, Kline RH, Forster MJ, Woolverton WL, Kopajtic TA, Newman AH: Dopamine transporter binding without cocaine-like behavioral effects: synthesis and evaluation of benztropine analogs alone and in combination with cocaine in rodents. Psychopharmacology (Berl). 2001 Apr;154(4):362-74. [11349389 ]
  2. Kulkarni SS, Kopajtic TA, Katz JL, Newman AH: Comparative structure-activity relationships of benztropine analogues at the dopamine transporter and histamine H(1) receptors. Bioorg Med Chem. 2006 Jun 1;14(11):3625-34. Epub 2006 Feb 3. [16460947 ]
  3. Reith ME, Berfield JL, Wang LC, Ferrer JV, Javitch JA: The uptake inhibitors cocaine and benztropine differentially alter the conformation of the human dopamine transporter. J Biol Chem. 2001 Aug 3;276(31):29012-8. Epub 2001 Jun 6. [11395483 ]
  4. Simoni D, Roberti M, Rondanin R, Baruchello R, Rossi M, Invidiata FP, Merighi S, Varani K, Gessi S, Borea PA, Marino S, Cavallini S, Bianchi C, Siniscalchi A: Effects of two-carbon bridge region methoxylation of benztropine: discovery of novel chiral ligands for the dopamine transporter. Bioorg Med Chem Lett. 2001 Mar 26;11(6):823-7. [11277529 ]
  5. Todd CL, Grace AA: Interaction of benztropine and haloperidol actions on rat substantia nigra dopamine cell electrophysiological activity in vivo. Brain Res Bull. 1999 Jan 15;48(2):219-22. [10230713 ]
  6. Zou MF, Kopajtic T, Katz JL, Wirtz S, Justice JB Jr, Newman AH: Novel tropane-based irreversible ligands for the dopamine transporter. J Med Chem. 2001 Dec 6;44(25):4453-61. [11728190 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular weight:
55783.6
References
  1. Kulkarni SS, Kopajtic TA, Katz JL, Newman AH: Comparative structure-activity relationships of benztropine analogues at the dopamine transporter and histamine H(1) receptors. Bioorg Med Chem. 2006 Jun 1;14(11):3625-34. Epub 2006 Feb 3. [16460947 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover
Gene Name:
CHRM1
Uniprot ID:
P11229
Molecular weight:
51420.4
References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]