DrugBank: Oxamniquine (DB01096)

targets (1) enzymes (1)

Identification

Name

Oxamniquine

Accession Number

DB01096 (APRD01150)

Type

small molecule

Groups

approved

Description

An anthelmintic with schistosomicidal activity against Schistosoma mansoni, but not against other Schistosoma spp. Oxamniquine causes worms to shift from the mesenteric veins to the liver where the male worms are retained; the female worms return to the mesentery, but can no longer release eggs. (From Martidale, The Extra Pharmacopoeia, 31st ed, p121)

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Not Available

Salts

Not Available

Brand names

Name	Company
Mansil
Vansil

Brand mixtures

Not Available

Categories

Schistosomicides

CAS number

21738-42-1

Weight

Average: 279.3348
Monoisotopic: 279.158291553

Chemical Formula

C₁₄H₂₁N₃O₃

InChI Key

InChIKey=XCGYUJZMCCFSRP-UHFFFAOYSA-N

InChI

InChI=1S/C14H21N3O3/c1-9(2)15-7-12-4-3-10-5-11(8-18)14(17(19)20)6-13(10)16-12/h5-6,9,12,15-16,18H,3-4,7-8H2,1-2H3

Plain Text

IUPAC Name

(7-nitro-2-{[(propan-2-yl)amino]methyl}-1,2,3,4-tetrahydroquinolin-6-yl)methanol

SMILES

CC(C)NCC1CCC2=CC(CO)=C(C=C2N1)[N+]([O-])=O

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Nitrobenzenes
Phenylpropylamines
(Iso)quinolines and Derivatives

Substructures

Hydroxy Compounds
Nitrobenzenes
Benzyl Alcohols and Derivatives
Oxoazaniums
Aliphatic and Aryl Amines
Benzene and Derivatives
Nitro compounds
Alcohols and Polyols
Heterocyclic compounds
Aromatic compounds
Phenylpropylamines
(Iso)quinolines and Derivatives
Anilines

Pharmacology

Indication

For treatment of Schistosomiasis caused by Schistosoma mansoni

Pharmacodynamics

Oxamniquine is an anthelmintic with schistosomicidal activity against Schistosoma mansoni, but not against other Schistosoma spp. Oxamniquine causes worms to shift from the mesenteric veins to the liver where the male worms are retained; the female worms return to the mesentery, but can no longer release egg.

Mechanism of action

Oxamniquine may associate with an irreversible inhibition of the nucleic acid metabolism of the parasites. A hypothesis has been put forth that the drug is activated by a single step, in which a schistosome sulfotransferase enzyme converts oxamniquine into an ester (probably acetate, phosphate, or sulfate). Subsequently, the ester spontaneously dissociates, the resulting electrophilic reactant is capable of alkylation of schistosome DNA.

Absorption

Well absorbed orally

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Probably hepatic

Route of elimination

Not Available

Half life

1-2.5 hours

Clearance

Not Available

Toxicity

Not Available

Affected organisms

Schistosoma mansoni

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Pfizer laboratories div pfizer inc

Packagers

Not Available

Dosage forms

Not Available

Prices

Not Available

Patents

Not Available

Properties

State

solid

Experimental Properties

Property	Value	Source
melting point	147-149 °C	PhysProp
water solubility	820 mg/L	Not Available
logP	2.24	SANGSTER (1993)

Predicted Properties

Property	Value	Source
water solubility	1.24e-01 g/l	ALOGPS
logP	1.54	ALOGPS
logP	1.57	ChemAxon
logS	-3.4	ALOGPS
pKa (strongest acidic)	14.55	ChemAxon
pKa (strongest basic)	9.9	ChemAxon
physiological charge	1	ChemAxon
hydrogen acceptor count	5	ChemAxon
hydrogen donor count	3	ChemAxon
polar surface area	90.11	ChemAxon
rotatable bond count	5	ChemAxon
refractivity	79.87	ChemAxon
polarizability	30.19	ChemAxon

References

Synthesis Reference

See General references, Filho et. al. for synthesis of oxamniquine methacylate.

General Reference

Filho RP, de Souza Menezes CM, Pinto PL, Paula GA, Brandt CA, da Silveira MA: Design, synthesis, and in vivo evaluation of oxamniquine methacrylate and acrylamide prodrugs. Bioorg Med Chem. 2007 Feb 1;15(3):1229-36. Epub 2006 Nov 16. Pubmed

External Links

Resource	Link
KEGG Drug	D00460
KEGG Compound	C07341
PubChem Compound	4612
PubChem Substance	46508789
ChemSpider	4451
Therapeutic Targets Database	DAP000992
PharmGKB	PA164748782
Drugs.com	http://www.drugs.com/mtm/oxamniquine.html
Wikipedia	http://en.wikipedia.org/wiki/Oxamniquine

ATC Codes

P02BA02

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

show (50 KB)

Interactions

Drug Interactions

Not Available

Food Interactions

Not Available

Targets
1. DNA Pharmacological action: yes Actions: other/unknown DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes. Gene Sequence: FASTA References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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 Pica-Mattoccia L, Carlini D, Guidi A, Cimica V, Vigorosi F, Cioli D: The schistosome enzyme that activates oxamniquine has the characteristics of a sulfotransferase. Mem Inst Oswaldo Cruz. 2006 Sep;101 Suppl 1:307-12. Pubmed

Targets

1. DNA

Pharmacological action: yes
Actions: other/unknown

DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.

Gene Sequence: FASTA

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
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
Pica-Mattoccia L, Carlini D, Guidi A, Cimica V, Vigorosi F, Cioli D: The schistosome enzyme that activates oxamniquine has the characteristics of a sulfotransferase. Mem Inst Oswaldo Cruz. 2006 Sep;101 Suppl 1:307-12. Pubmed

Enzymes
1. Cytochrome P450 2D6 Actions: inhibitor 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 UniProt ID: P10635 Gene: CYP2D6 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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. Pubmed

Enzymes

1. Cytochrome P450 2D6

Actions: inhibitor

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

UniProt ID: P10635 Link_out

Gene: CYP2D6 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19