Identification

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Name
Benzatropine
Accession Number
DB00245  (APRD00748)
Type
Small Molecule
Groups
Approved
Description

Benztropine, with the chemical formula 3alpha-diphenylmethoxytropane, is a tropane-based dopamine inhibitor used for the symptomatic treatment of Parkinson's disease. It is a combination molecule between a tropane ring, similar to cocaine, and a diphenyl ether from the dialkylpiperazines determined to be a dopamine uptake inhibitor since 1970. The generation of structure-activity relationships proved that benztropine derivatives with the presence of a chlorine substituent in the para position in one of the phenyl rings produces an increased potency for dopamine uptake inhibition as well as a decreased inhibition of serotonin and norepinephrine.[1] Benztropine was developed by USL Pharma and officially approved by the FDA on 1996.[9]

Structure
Thumb
Synonyms
  • 3-alpha-(diphenylmethoxy)tropane
  • 3endo-benzhydryloxytropane
  • 3α-(diphenylmethoxy)-1αH,5αH-tropane
  • 3α-(diphenylmethoxy)tropane
  • 3α-benzhydryloxy-8-methyl-8-azabicyclo[3.2.1]octane
  • Benzatropina
  • Benzatropine
  • Benzatropinum
  • benzhydryl 8-methyl-8-azabicyclo[3.2.1]oct-3-yl ether
  • Benztropine
  • Tropine benzohydryl ether
External IDs
NK-02
Product Ingredients
IngredientUNIICASInChI Key
Benzatropine mesylateWMJ8TL7510132-17-2CPFJLLXFNPCTDW-BWSPSPBFSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Bensylate Tab 2mgTablet2 mgOralIcn Pharmaceuticals1978-12-312005-04-26Canada
Benztropine 2 Tab 2mgTablet2 mgOralPro Doc Limitee1982-12-312009-07-23Canada
Benztropine Mesylate Injection, USPLiquid1 mgIntramuscular; IntravenousSabex IncNot applicableNot applicableCanada
Benztropine OmegaLiquid1 mgIntramuscular; IntravenousOmega Laboratories Ltd1999-05-28Not applicableCanada
CogentinInjection1 mg/1mLIntramuscular; IntravenousOak Pharmaceuticals, Inc. (Subsidiary of Akorn, Inc.)1959-08-05Not applicableUs
CogentinInjection, solution1 mg/1mLIntramuscular; IntravenousLundbeck Inc.1959-08-052011-12-22Us
Cogentin Inj 1mg/mlSolution1 mgIntramuscular; IntravenousMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1959-12-312004-07-29Canada
Cogentin Tab 2mgTablet2 mgOralMerck Frosst Canada & Cie, Merck Frosst Canada & Co.1954-12-312003-01-29Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BenztropineTablet1 mg/1OralContract Pharmacy Services-PA2017-04-13Not applicableUs
Benztropine MesylateInjection1 mg/1mLIntramuscular; IntravenousTYA Pharmaceuticals2012-08-08Not applicableUs
Benztropine MesylateTablet0.5 mg/1OralAmerican Health Packaging2018-08-31Not applicableUs
Benztropine MesylateTablet1 mg/1OralAmerican Health Packaging2018-04-03Not applicableUs
Benztropine MesylateTablet1 mg/1OralRemedy Repack2011-01-122012-03-07Us
Benztropine MesylateTablet1 mg/1OralREMEDYREPACK INC.2017-11-30Not applicableUs
Benztropine MesylateTablet2 mg/1OralAmerican Health Packaging2018-04-04Not applicableUs
Benztropine MesylateTablet1 mg/1OralState of Florida DOH Central Pharmacy2009-07-01Not applicableUs64980 0112 01 nlmimage10 dc236e0b
Benztropine MesylateTablet1 mg/1OralPd Rx Pharmaceuticals, Inc.2010-02-282017-07-11Us
Benztropine MesylateTablet0.5 mg/1OralMarlex Pharmaceuticals Inc2017-12-15Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Benztropine MesylateBenzatropine mesylate (0.5 mg/1)TabletOralRemedy Repack2011-09-062011-10-20Us50111 0393 01 nlmimage10 61233089
International/Other Brands
Apo-Benztropine (Apotex) / Cogentinol (Astra (Germany, discontinued)) / PMS Benztropine (Pharmascience)
Categories
UNII
1NHL2J4X8K
CAS number
86-13-5
Weight
Average: 307.4293
Monoisotopic: 307.193614427
Chemical Formula
C21H25NO
InChI Key
GIJXKZJWITVLHI-PMOLBWCYSA-N
InChI
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+
IUPAC Name
(1R,3R,5S)-3-(diphenylmethoxy)-8-methyl-8-azabicyclo[3.2.1]octane
SMILES
[H][C@]12CC[C@]([H])(C[C@@]([H])(C1)OC(C1=CC=CC=C1)C1=CC=CC=C1)N2C

Pharmacology

Indication

Benztropine is indicated to be used as an adjunct in the therapy of all forms of parkinsonism. It can also be used for the control of extrapyramidal disorders due to neuroleptic drugs.[7]

The extrapyramidal symptoms are defined as drug-induced disorders that include symptoms of dystonia, akathisia, parkinsonism, bradykinesia, tremors, and dyskinesia.[4]

Parkinsonism is a general term that refers to the group of neurological disorders that produce symptoms similar to Parkinson's disease such as tremors, slow movement, and stiffness. The parkinsonism includes a large number of disorders and some of them have not been clearly defined.[10]

Associated Conditions
Pharmacodynamics

The inhibition of dopamine reuptake by benztropine produces a dose-dependent increase of dopamine in the nerve terminal of the dopaminergic system.[5]

Clinically the activity of benztropine is observed after 1-2 hours of oral administration and after a few minutes of intramuscular administration with a last-longing effect of about 24 hours. Reports have indicated that benztropine has a very large sedative effect.[5]

The antihistaminic effect of benztropine is very similar to the effect found in pyrilamine and the anticholinergic activity was found to be equal to atropine ex vivo and of about 50% activity in vivo.[11]

Mechanism of action

Benztropine is an agent with anti-muscarinic and antihistaminic effects. Its main mechanism of action is presented by the selective inhibition of dopamine transporters but it also presents affinity for histamine and muscarine receptors.[2]

It is widely known that benztropine is a potent inhibitor of presynaptic carrier-mediated dopamine transport. As well, it is known to be an analog of atropine and hence, it has a large affinity for muscarinic receptors M1 in the human brain. Once bound, benztropine blocks the activity of the muscarinic receptors mainly in the striatum.[5]

The increased advantage of benztropine lays on the antagonism of acetylcholine activity which corrects the imbalance between dopamine and acetylcholine in Parkinson patients.[11]

TargetActionsOrganism
AMuscarinic acetylcholine receptor M1
antagonist
Humans
ASodium-dependent dopamine transporter
inhibitor
Humans
UHistamine H1 receptor
antagonist
Humans
NSodium-dependent serotonin transporter
inhibitor
Humans
NSodium-dependent noradrenaline transporter
inhibitor
Humans
Absorption

Oral administration of 1.5 mg of benztropine is slowly absorbed in the gastrointestinal tract and it reaches a peak concentration of 2.5 ng/ml in about 7 hours.[3] It has an approximate oral bioavailability of 29%.[8]

Volume of distribution

Benztropine is expected to present a large volume of distribution between 12-30 L/kg.[6]

Protein binding

About 95% of the administered dose of benztropine is found bound to plasma proteins.[8]

Metabolism

Benztropine has been shown to undergo metabolism mainly marked by N-oxidation, N-dealkylation and ring hydroxylation.[3] The extensive metabolism of benztropine produces eight phase-I metabolites plus four glucuronide conjugates.[5]

Route of elimination

Benztropine is mainly excreted in the urine but it is also found in the feces unchanged.[5]

Half life

The elimination half-life of benztropine is very variable and it is reported to be of around 36 hours.[12]

Clearance

Extensive pharmacodynamic or pharmacokinetic studies have not been performed.

Toxicity

The oral LD50 of benztropine is reported to be of 940 mg/kg in rats.[MSDS] In the presence of overdose with benztropine, it has been observed symptoms of circulatory collapse, cardiac arrest, respiratory depression, respiratory arrest, psychosis, shock, coma, seizure, ataxia, combativeness, anhidrosis, hyperthermia, fever, dysphagia, decreased bowel sounds and sluggish pupils.[12]

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Benzatropine can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Benzatropine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Benzatropine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Benzatropine.
4-Methoxyamphetamine4-Methoxyamphetamine may increase the central nervous system depressant (CNS depressant) activities of Benzatropine.
7-Nitroindazole7-Nitroindazole may increase the central nervous system depressant (CNS depressant) activities of Benzatropine.
AbacavirBenzatropine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbataceptThe metabolism of Benzatropine can be increased when combined with Abatacept.
AbediterolThe risk or severity of Tachycardia can be increased when Benzatropine is combined with Abediterol.
AbexinostatThe risk or severity of QTc prolongation can be increased when Benzatropine is combined with Abexinostat.
Food Interactions
  • Avoid alcohol.
  • Take with food to reduce irritation.

References

General References
  1. Rothman RB, Baumann MH, Prisinzano TE, Newman AH: Dopamine transport inhibitors based on GBR12909 and benztropine as potential medications to treat cocaine addiction. Biochem Pharmacol. 2008 Jan 1;75(1):2-16. doi: 10.1016/j.bcp.2007.08.007. Epub 2007 Aug 9. [PubMed:17897630]
  2. Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, Partilla JS, Rothman RB, Katz JL: Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter. Drug Alcohol Depend. 2015 Feb 1;147:1-19. doi: 10.1016/j.drugalcdep.2014.12.005. Epub 2014 Dec 18. [PubMed:25548026]
  3. Brocks DR: Anticholinergic drugs used in Parkinson's disease: An overlooked class of drugs from a pharmacokinetic perspective. J Pharm Pharm Sci. 1999 May-Aug;2(2):39-46. [PubMed:10952768]
  4. Blair DT, Dauner A: Extrapyramidal symptoms are serious side-effects of antipsychotic and other drugs. Nurse Pract. 1992 Nov;17(11):56, 62-4, 67. [PubMed:1359485]
  5. Deleu D, Northway MG, Hanssens Y: Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson's disease. Clin Pharmacokinet. 2002;41(4):261-309. [PubMed:11978145]
  6. Raje S, Cao J, Newman AH, Gao H, Eddington ND: Evaluation of the blood-brain barrier transport, population pharmacokinetics, and brain distribution of benztropine analogs and cocaine using in vitro and in vivo techniques. J Pharmacol Exp Ther. 2003 Nov;307(2):801-8. doi: 10.1124/jpet.103.053504. Epub 2003 Sep 9. [PubMed:12966155]
  7. Troy B. and Beringer P. (2006). Remington: The Science and Practice of Pharmacy (21st ed.). Lippincott Williams & Wilkins.
  8. Hale T. and Rowe H. (2017). MEdications & mothers' milk (17th ed.). Springer publishing company. [ISBN:978-0-8261-2858-4]
  9. FDA approvals [Link]
  10. Parkinson [Link]
  11. pdp-BENZTROPINE (benztropine) Prescribing information [File]
  12. Benztropine informational sheet [File]
External Links
Human Metabolome Database
HMDB0014390
KEGG Drug
D07511
KEGG Compound
C06846
PubChem Compound
1201549
PubChem Substance
46505349
ChemSpider
16736541
BindingDB
50366775
ChEBI
3048
ChEMBL
CHEMBL1201203
Therapeutic Targets Database
DAP001460
PharmGKB
PA448591
HET
CXQ
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Benztropine
ATC Codes
N04AC01 — Benzatropine
AHFS Codes
  • 28:36.08 — Anticholinergic Agents
PDB Entries
6f6s
FDA label
Download (54.9 KB)
MSDS
Download (73.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentBack Pain1
2CompletedTreatmentBack Pain / Sciatica1
2CompletedTreatmentCocaine-Related Disorders1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Peripheral Nervous System Diseases1
4CompletedTreatmentAcute Agitation1
4CompletedTreatmentSchizophrenic Disorders1
Not AvailableTerminatedTreatmentDelusional Disorder / Psychotic Disorder NOS / Schizoaffective Disorders / Schizophrenic Disorders / Schizophreniform Disorder1

Pharmacoeconomics

Manufacturers
  • Hikma farmaceutica (portugal) sa
  • Nexus pharmaceuticals inc
  • Pharmaforce inc
  • Lundbeck inc
  • Actavis totowa llc
  • Corepharma llc
  • Invagen pharmaceuticals inc
  • Lannett holdings inc
  • Mutual pharmaceutical co inc
  • Pliva inc
  • Quantum pharmics ltd
  • Usl pharma inc
  • Vintage pharmaceuticals llc
  • Merck and co inc
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • Amneal Pharmaceuticals
  • AQ Pharmaceuticals Inc.
  • Cardinal Health
  • Comprehensive Consultant Services Inc.
  • Corepharma LLC
  • Coupler Enterprises Inc.
  • Dept Health Central Pharmacy
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Goldline Laboratories Inc.
  • Heartland Repack Services LLC
  • Hikma Pharmaceuticals
  • Ivax Pharmaceuticals
  • Liberty Pharmaceuticals
  • Lundbeck Inc.
  • Major Pharmaceuticals
  • Medisca Inc.
  • Merck & Co.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Neuman Distributors Inc.
  • Nexus Pharmaceuticals
  • Nucare Pharmaceuticals Inc.
  • PCA LLC
  • Pharmaceutical Packaging Center
  • Pharmedix
  • Physicians Total Care Inc.
  • Pliva Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Qualitest
  • Rebel Distributors Corp.
  • Remedy Repack
  • Rising Pharmaceuticals
  • Sandhills Packaging Inc.
  • Schein Pharmaceutical Inc.
  • Southwood Pharmaceuticals
  • Tya Pharmaceuticals
  • UDL Laboratories
  • United Research Laboratories Inc.
  • USL Pharma Inc.
  • Vangard Labs Inc.
  • Vintage Pharmaceuticals Inc.
  • West-Ward Pharmaceuticals
Dosage forms
FormRouteStrength
InjectionIntramuscular; Intravenous1 mg/1mL
Injection, solutionIntramuscular; Intravenous1 mg/1mL
TabletOral0.5 mg/1
TabletOral1 mg/1
TabletOral2 mg/1
InjectionParenteral1 mg/1mL
LiquidIntramuscular; Intravenous1 mg
SolutionIntramuscular; Intravenous1 mg
TabletOral2 mg
SolutionOral2 mg
TabletOral1 mg
TabletOral0.5 mg
Prices
Unit descriptionCostUnit
Cogentin 2 mg/2 ml ampule70.09USD ml
Benztropine 2 mg/2 ml ampule37.5USD ml
Benztropine 2 mg/2 ml vial33.0USD ml
Benztropine mesylate powder26.38USD g
Benztropine mes 2 mg tablet0.41USD tablet
Benztropine mes 1 mg tablet0.38USD tablet
Benztropine mes 0.5 mg tablet0.34USD tablet
Benztropine Mesylate 0.5 mg tablet0.27USD tablet
Benztropine Mesylate 1 mg tablet0.27USD tablet
Benztropine Mesylate 2 mg tablet0.26USD tablet
Apo-Benztropine 2 mg Tablet0.06USD tablet
Pms-Benztropine 2 mg Tablet0.05USD tablet
Pms-Benztropine 1 mg Tablet0.02USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)135ºC'MSDS'
boiling point (°C)547.8 ºC at 760 mm HgCAS
water solubility81 mg/ml'MSDS'
logP4.27Xu A. and Madden T. 2012. LC-MS in Drug Bioanalysis.
pKa10Troy D. and Beringer P. 2006. Remington: The Science and Practice of Pharmacy.
Predicted Properties
PropertyValueSource
Water Solubility0.00121 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 RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9766
Blood Brain Barrier+0.9929
Caco-2 permeable+0.7912
P-glycoprotein substrateNon-substrate0.5145
P-glycoprotein inhibitor IInhibitor0.8428
P-glycoprotein inhibitor IINon-inhibitor0.9561
Renal organic cation transporterInhibitor0.8218
CYP450 2C9 substrateNon-substrate0.7188
CYP450 2D6 substrateNon-substrate0.5
CYP450 3A4 substrateSubstrate0.669
CYP450 1A2 substrateNon-inhibitor0.9383
CYP450 2C9 inhibitorNon-inhibitor0.9072
CYP450 2D6 inhibitorInhibitor0.7739
CYP450 2C19 inhibitorNon-inhibitor0.871
CYP450 3A4 inhibitorNon-inhibitor0.9627
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8925
Ames testNon AMES toxic0.5994
CarcinogenicityNon-carcinogens0.9729
BiodegradationNot ready biodegradable0.8768
Rat acute toxicity2.5708 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6077
hERG inhibition (predictor II)Non-inhibitor0.534
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
Tropane alkaloids / Benzylethers / Piperidines / N-alkylpyrrolidines / Trialkylamines / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Diphenylmethane / Benzylether / Tropane alkaloid / Piperidine / N-alkylpyrrolidine / Pyrrolidine / Tertiary amine / Tertiary aliphatic amine / Dialkyl ether / Ether
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tertiary amino compound (CHEBI:3048)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
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...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 Da
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. [PubMed: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. [PubMed:17139284]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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
Uniprot Name
Sodium-dependent dopamine transporter
Molecular Weight
68494.255 Da
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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:11728190]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
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 catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
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. [PubMed:16460947]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Serotonin: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 t...
Gene Name
SLC6A4
Uniprot ID
P31645
Uniprot Name
Sodium-dependent serotonin transporter
Molecular Weight
70324.165 Da
References
  1. Rothman RB, Baumann MH, Prisinzano TE, Newman AH: Dopamine transport inhibitors based on GBR12909 and benztropine as potential medications to treat cocaine addiction. Biochem Pharmacol. 2008 Jan 1;75(1):2-16. doi: 10.1016/j.bcp.2007.08.007. Epub 2007 Aug 9. [PubMed:17897630]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Norepinephrine: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
Uniprot Name
Sodium-dependent noradrenaline transporter
Molecular Weight
69331.42 Da
References
  1. Rothman RB, Baumann MH, Prisinzano TE, Newman AH: Dopamine transport inhibitors based on GBR12909 and benztropine as potential medications to treat cocaine addiction. Biochem Pharmacol. 2008 Jan 1;75(1):2-16. doi: 10.1016/j.bcp.2007.08.007. Epub 2007 Aug 9. [PubMed:17897630]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase 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 im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Othman AA, Syed SA, Newman AH, Eddington ND: Transport, metabolism, and in vivo population pharmacokinetics of the chloro benztropine analogs, a class of compounds extensively evaluated in animal models of drug abuse. J Pharmacol Exp Ther. 2007 Jan;320(1):344-53. doi: 10.1124/jpet.106.111245. Epub 2006 Sep 26. [PubMed:17003230]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase 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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Othman AA, Syed SA, Newman AH, Eddington ND: Transport, metabolism, and in vivo population pharmacokinetics of the chloro benztropine analogs, a class of compounds extensively evaluated in animal models of drug abuse. J Pharmacol Exp Ther. 2007 Jan;320(1):344-53. doi: 10.1124/jpet.106.111245. Epub 2006 Sep 26. [PubMed:17003230]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Hale T. and Rowe H. (2017). MEdications & mothers' milk (17th ed.). Springer publishing company. [ISBN:978-0-8261-2858-4]

Drug created on June 13, 2005 07:24 / Updated on April 21, 2019 05:09