Details of the Drug

General Information of Drug (ID: DMF7EXL)

• Drug Name: Benzatropine
• Synonyms: Benzatropina; Benzatropina [INN-Spanish]; Benzatropine; Benzatropinum; Benzatropinum [INN-Latin]; Benztropinum; Cobrentin; Cogentin; Cogentine; Akitan; Cogentinol; Tropine benzohydryl ether; benztropine; (3-endo)-3-(diphenylmethoxy)-8-methyl-8-azabicyclo[3.2.1]octane; 1NHL2J4X8K; 3alpha-(Diphenylmethoxy)-1alphaH,5alphaH-tropane; 3alpha-(diphenylmethoxy)tropane; 3alpha-benzhydryloxy-8-methyl-8-azabicyclo[3.2.1]octane; 3endo-benzhydryloxytropane; 86-13-5; CHEBI:3048; HSDB 3014; NCGC00159471-02; NK 02; UNII-1NHL2J4X8K

Indication

Disease Entry	ICD 11	Status	REF
Psychomotor agitation	MB23.M	Approved	[1]

• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 307.4
  Topological Polar Surface Area (xlogp); 4.5
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 2
• ADMET Property:
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 30-60 min [2]
  Bioavailability: The bioavailability of drug is 40% [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 36 hours [3]
  Metabolism: The drug is metabolized via N-oxidation, N-dealkylation and ring hydroxylation [4]
  Vd: The volume of distribution (Vd) of drug is 12-30 L/kg [5]
• Chemical Identifiers:
  Formula: C21H25NO
  IUPAC Name: (1R,5S)-3-benzhydryloxy-8-methyl-8-azabicyclo[3.2.1]octane
  Canonical SMILES: CN1C2CCC1CC(C2)OC(C3=CC=CC=C3)C4=CC=CC=C4
  InChI: GIJXKZJWITVLHI-YOFSQIOKSA-N
  InChIKey: 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?
• Cross-matching ID:
  PubChem CID: 1201549
  ChEBI ID: CHEBI:3048
  CAS Number: 86-13-5
  DrugBank ID: DB00245
  INTEDE ID: DR0192

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Substrate	[6]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Substrate	[6]

References

• [1] Benzatropine was approved by FDA. The 2020 official website of the U.S. Food and Drug Administration.
• [2] Dihydroergotamine, ergotamine, methysergide and sumatriptan - basic science in relation to migraine treatment. Headache. 2012 Apr;52(4):707-14. doi: 10.1111/j.1526-4610.2012.02124.x. Epub 2012 Mar 22.
• [3] FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
• [4] Matzke GR, Zhanel GG, Guay DR: Clinical pharmacokinetics of vancomycin. Clin Pharmacokinet. 1986 Jul-Aug;11(4):257-82. doi: 10.2165/00003088-198611040-00001.
• [5] 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.
• [6] 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.
• [7] Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
• [8] Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
• [9] CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
• [10] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [11] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [12] Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
• [13] Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
• [14] Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
• [15] Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
• [16] Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
• [17] High-dose rabeprazole/amoxicillin therapy as the second-line regimen after failure to eradicate H. pylori by triple therapy with the usual doses of a proton pump inhibitor, clarithromycin and amoxicillin. Hepatogastroenterology. 2003 Nov-Dec;50(54):2274-8.
• [18] Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
• [19] Cytochrome P450 pharmacogenetics and cancer. Oncogene. 2006 Mar 13;25(11):1679-91.
• [20] CYP2C19*17 is associated with decreased breast cancer risk. Breast Cancer Res Treat. 2009 May;115(2):391-6.
• [21] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [22] Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):116-21.
• [23] Diclofenac and its derivatives as tools for studying human cytochromes P450 active sites: particular efficiency and regioselectivity of P450 2Cs. Biochemistry. 1999 Oct 26;38(43):14264-70.
• [24] A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
• [25] Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver. Gastroenterology. 2001 Feb;120(2):525-33.
• [26] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.