Benzatropine (T3D2724)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (3)XML
Targets (3)
Record Information
Version2.0
Creation Date2009-07-21 20:26:23 UTC
Update Date2014-12-24 20:25:50 UTC
Accession NumberT3D2724
Identification
Common NameBenzatropine
ClassSmall Molecule
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.
Compound Type
  • Amine
  • Antidyskinetic
  • Antiparkinson Agent
  • Dopamine Uptake Inhibitor
  • Drug
  • Ether
  • Metabolite
  • Muscarinic Antagonist
  • Organic Compound
  • Parasympatholytic
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
3-alpha-(diphenylmethoxy)tropane
3alpha-(Diphenylmethoxy)-1alphah,5alphah-tropane
3alpha-(Diphenylmethoxy)tropane
3alpha-Benzhydryloxy-8-methyl-8-azabicyclo[3.2.1]octane
3endo-benzhydryloxytropane
3α-(diphenylmethoxy)-1αH,5αH-tropane
3α-(diphenylmethoxy)tropane
3α-benzhydryloxy-8-methyl-8-azabicyclo[3.2.1]octane
Apo-Benztropine
Benzatropina
Benzatropine mesilate
Benzatropinum
Benzhydryl 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ether
Benztropine
Benztropinum
Cogentin
Cogentinol
PMS Benztropine
Tropine Benzohydryl Ether
Chemical FormulaC21H25NO
Average Molecular Mass307.429 g/mol
Monoisotopic Mass307.194 g/mol
CAS Registry Number86-13-5
IUPAC Name(1R,3R,5S)-3-(diphenylmethoxy)-8-methyl-8-azabicyclo[3.2.1]octane
Traditional Namebenzatropina
SMILES[H][C@]12CC[C@]([H])(C[C@@]([H])(C1)OC(C1=CC=CC=C1)C1=CC=CC=C1)N2C
InChI IdentifierInChI=1/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-PMOLBWCYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as diphenylmethanes. Diphenylmethanes 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
  • Benzylether
  • Tropane alkaloid
  • Piperidine
  • N-alkylpyrrolidine
  • Pyrrolidine
  • Tertiary amine
  • Tertiary aliphatic amine
  • Dialkyl ether
  • Ether
  • Azacycle
  • Organoheterocyclic compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point138-140°C
Boiling PointNot Available
SolubilityVery soluble
LogP4.3
Predicted Properties
PropertyValueSource
Water Solubility0.0012 g/LALOGPS
logP4.47ALOGPS
logP4.19ChemAxon
logS-5.4ALOGPS
pKa (Strongest Basic)9.54ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.47 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity94.24 m³·mol⁻¹ChemAxon
Polarizability35.42 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-014i-7910000000-522d5f59ab66fd4918652017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0309000000-128b2c78aa7b0dd7d9e52016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0avi-1914000000-96ca5c9a7aea2b463b4d2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00rt-9600000000-6dda6384a6abcbd56c1f2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0209000000-6ac5128c1f553f581afd2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-1619000000-5e54998dd75131048af52016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-6900000000-e13c6d55b6124ce3b7332016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0009000000-362958de4b63235619b62021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0809000000-7234c053d550e60a1abd2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a59-0910000000-e6dc1d8e76e7c2a1274e2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0009000000-f64e7cf22237a4e2aed02021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-0309000000-9c52d4b915a455b8641a2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014i-1900000000-ea82f96932aa4d0549882021-09-22View Spectrum
Toxicity Profile
Route of ExposureIntravenous, Oral. Onset of action is 1-2 hours following oral administration. The onset of action is within minutes when administered by IM or IV injection.
Mechanism of ToxicityBenztropine is a selective M1 muscarinic acetylcholine receptor antagonist. It is able to discriminate between the M1 (cortical or neuronal) and the peripheral muscarinic subtypes (cardiac and glandular). Benztropine partially blocks cholinergic activity in the CNS, which is responsible for the symptoms of Parkinson's disease. It is also thought to increase the availability of dopamine, a brain chemical that is critical in the initiation and smooth control of voluntary muscle movement.
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor use as an adjunct in the therapy of all forms of parkinsonism and also for use in the control of extrapyramidal disorders due to neuroleptic drugs.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSigns of overdose include confusion, nervousness, listlessness, hallucinations, dizziness; muscle weakness, ataxia, dry mouth, mydriasis, blurred vision, palpitations, tachycardia, elevated blood pressure, nausea, vomiting, dysuria, numbness of fingers, headache, delirium, coma, shock, convulsions, respiratory arrest, anhidrosis, hyperthermia, glaucoma, and constipation.
TreatmentPhysostigmine salicylate, 1 to 2 mg, SC or IV, reportedly will reverse symptoms of anticholinergic intoxication. A second injection may be given after 2 hours if required. Otherwise treatment is symptomatic and supportive. Induce emesis or perform gastric lavage (contraindicated in precomatose, convul-sive, or psychotic states). Maintain respiration. A short-acting barbiturate may be used for CNS excitement, but with caution to avoid subsequent depression; supportive care for depression (avoid convulsant stimulants such as picrotoxin, pentylenetetrazol, or bemegride); artificial respiration for severe respiratory depression; a local miotic for mydriasis and cycloplegia; ice bags or other cold applications and alcohol sponges for hyperpyrexia, a vasopressor and fluids for circulatory collapse. Darken room for photophobia. (4)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00245
HMDB IDHMDB14390
PubChem Compound ID6832
ChEMBL IDNot Available
ChemSpider ID16736541
KEGG IDC06846
UniProt IDNot Available
OMIM ID
ChEBI ID3048
BioCyc IDNot Available
CTD IDNot Available
Stitch IDBenztropine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkBenztropine
References
Synthesis Reference

Phillips, R.F.; US. Patent 2,595,405; May 6, 1952; assigned to Merck & Co., Inc.

MSDSLink
General References
  1. 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 ]
  2. 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 ]
  3. Drugs.com [Link]
  4. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Sodium-dependent dopamine transporter
General Function:
Monoamine transmembrane transporter 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 Da
References
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
Target Details
2. Muscarinic acetylcholine receptor M1
General Function:
Phosphatidylinositol phospholipase c activity
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:
51420.375 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. 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 ]
Target Details
3. Histamine H1 receptor
General Function:
Histamine receptor activity
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:
55783.61 Da
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 ]