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Identification
NameNizatidine
Accession NumberDB00585  (APRD00706)
Typesmall molecule
Groupsapproved
Description

A histamine H2 receptor antagonist with low toxicity that inhibits gastric acid secretion. The drug is used for the treatment of duodenal ulcers. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
NizatidinaSpanishNot Available
NizatidineNot AvailableINN, BAN, USAN, JAN
NizatidinumLatinNot Available
SaltsNot Available
Brand names
NameCompany
AcinonNot Available
AxidEli Lilly
TazacEli Lilly
Brand mixturesNot Available
Categories
CAS number76963-41-2
WeightAverage: 331.457
Monoisotopic: 331.113666321
Chemical FormulaC12H21N5O2S2
InChI KeyInChIKey=SGXXNSQHWDMGGP-IZZDOVSWSA-N
InChI
InChI=1S/C12H21N5O2S2/c1-13-11(6-17(18)19)14-4-5-20-8-10-9-21-12(15-10)7-16(2)3/h6,9,13-14H,4-5,7-8H2,1-3H3/b11-6+
IUPAC Name
dimethyl[(4-{[(2-{[(E)-1-(methylamino)-2-nitroethenyl]amino}ethyl)sulfanyl]methyl}-1,3-thiazol-2-yl)methyl]amine
SMILES
CN\C(NCCSCC1=CSC(CN(C)C)=N1)=C/[N+]([O-])=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassAzoles
SubclassThiazoles
Direct parent2,4-disubstituted Thiazoles
Alternative parentsNitro Compounds; Tertiary Amines; Nitronic Acids; Polyamines; Organic Oxoazanium Compounds; Thioethers
Substituentsnitronic acid; nitro compound; tertiary amine; organic oxoazanium; polyamine; thioether; amine; organonitrogen compound
Classification descriptionThis compound belongs to the 2,4-disubstituted thiazoles. These are compounds containing a thiazole ring substituted at positions 2 and 4 only.
Pharmacology
IndicationFor the treatment of acid-reflux disorders (GERD), peptic ulcer disease, active benign gastric ulcer, and active duodenal ulcer.
PharmacodynamicsNizatidine is a competitive, reversible inhibitor of histamine at the histamine H2-receptors, particularly those in the gastric parietal cells. By inhibiting the action of histamine on stomach cells, nizatidine reduces stomach acid production. Nizatidine had no demonstrable antiandrogenic action. Full-dose therapy for the problems treated by nizatidine lasts no longer than 8 weeks. It has been demonstrated that treatment with a reduced dose of nizatidine is effective as maintenance therapy following healing of active duodenal ulcers.
Mechanism of actionNizatidine competes with histamine for binding at the H2-receptors on the gastric basolateral membrane of parietal cells. Competitive inhibition results in reduction of basal and nocturnal gastric acid secretions. The drug also decreases the gastric acid response to stimuli such as food, caffeine, insulin, betazole, or pentagastrin.
AbsorptionRapid (bioavailability of nizatidine exceeds 70%)
Volume of distribution
  • 0.8 to 1.5 L/kg
Protein binding35%
Metabolism

Hepatic. Less than 7% of an oral dose is metabolized as N2-monodes-methylnizatidine, an H2-receptor antagonist, which is the principal metabolite excreted in the urine. Other likely metabolites are the N2-oxide (less than 5% of the dose) and the S-oxide (less than 6% of the dose).

SubstrateEnzymesProduct
Nizatidine
    N2-monodes-methylnizatidineDetails
    Route of eliminationNot Available
    Half life1-2 hours
    Clearance
    • 40-60 L/h
    • 7 – 14 L/h [functionally anephric patients]
    ToxicityOral, rat LD50: 301 mg/kg. Symptoms of overdose include cholinergic-type effects including lacrimation, salivation, emesis, miosis, and diarrhea.
    Affected organisms
    • Humans and other mammals
    Pathways
    PathwayCategorySMPDB ID
    Nizatidine Action PathwayDrug actionSMP00233
    SNP Mediated EffectsNot Available
    SNP Mediated Adverse Drug ReactionsNot Available
    ADMET
    Predicted ADMET features
    Property Value Probability
    Human Intestinal Absorption + 0.9572
    Blood Brain Barrier + 0.5
    Caco-2 permeable - 0.589
    P-glycoprotein substrate Substrate 0.8357
    P-glycoprotein inhibitor I Non-inhibitor 0.8947
    P-glycoprotein inhibitor II Non-inhibitor 0.8861
    Renal organic cation transporter Non-inhibitor 0.7832
    CYP450 2C9 substrate Non-substrate 0.8108
    CYP450 2D6 substrate Non-substrate 0.6721
    CYP450 3A4 substrate Non-substrate 0.5916
    CYP450 1A2 substrate Non-inhibitor 0.9045
    CYP450 2C9 substrate Non-inhibitor 0.9072
    CYP450 2D6 substrate Non-inhibitor 0.9231
    CYP450 2C19 substrate Non-inhibitor 0.9025
    CYP450 3A4 substrate Non-inhibitor 0.8508
    CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7826
    Ames test Non AMES toxic 0.6129
    Carcinogenicity Non-carcinogens 0.9182
    Biodegradation Not ready biodegradable 0.9295
    Rat acute toxicity 2.4350 LD50, mol/kg Not applicable
    hERG inhibition (predictor I) Strong inhibitor 0.6244
    hERG inhibition (predictor II) Non-inhibitor 0.8734
    Pharmacoeconomics
    Manufacturers
    • Smithkline beecham corp dba glaxosmithkline
    • Apotex inc
    • Dr reddys laboratories ltd
    • Genpharm inc
    • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
    • Mylan pharmaceuticals inc
    • Sandoz inc
    • Teva pharmaceuticals usa inc
    • Watson laboratories inc
    • Braintree laboratories inc
    • Amneal pharmaceuticals
    • Wyeth consumer healthcare
    Packagers
    Dosage forms
    FormRouteStrength
    CapsuleOral
    Prices
    Unit descriptionCostUnit
    Axid 300 mg pulvule6.0USDeach
    Nizatidine 300 mg capsule4.97USDcapsule
    Axid 300 mg Capsule3.98USDcapsule
    Axid 150 mg pulvule3.62USDeach
    Nizatidine 150 mg capsule2.48USDcapsule
    Axid 150 mg Capsule2.06USDcapsule
    Apo-Nizatidine 300 mg Capsule0.96USDcapsule
    Novo-Nizatidine 300 mg Capsule0.96USDcapsule
    Pms-Nizatidine 300 mg Capsule0.96USDcapsule
    Axid 15 mg/ml Solution0.84USDml
    Nizatidine 15 mg/ml Solution0.76USDml
    Apo-Nizatidine 150 mg Capsule0.53USDcapsule
    Gen-Nizatidine 150 mg Capsule0.53USDcapsule
    Novo-Nizatidine 150 mg Capsule0.53USDcapsule
    Pms-Nizatidine 150 mg Capsule0.53USDcapsule
    Axid ar 75 mg tablet0.3USDtablet
    DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
    Patents
    CountryPatent NumberApprovedExpires (estimated)
    United States69301192002-07-172022-07-17
    Properties
    Statesolid
    Experimental Properties
    PropertyValueSource
    melting point130-132 °CPhysProp
    water solubility10-33mg/mLNot Available
    logP1.1Not Available
    Predicted Properties
    PropertyValueSource
    water solubility3.86e-02 g/lALOGPS
    logP0.7ALOGPS
    logP0.76ChemAxon
    logS-3.9ALOGPS
    pKa (strongest basic)6.83ChemAxon
    physiological charge0ChemAxon
    hydrogen acceptor count6ChemAxon
    hydrogen donor count2ChemAxon
    polar surface area86.01ChemAxon
    rotatable bond count10ChemAxon
    refractivity96.84ChemAxon
    polarizability35.49ChemAxon
    number of rings1ChemAxon
    bioavailability1ChemAxon
    rule of fiveYesChemAxon
    Ghose filterYesChemAxon
    Veber's ruleNoChemAxon
    MDDR-like ruleNoChemAxon
    Spectra
    SpectraNot Available
    References
    Synthesis Reference

    Charles W. Ryan, Bruce A. Slomski, “Synthesis of nizatidine intermediate.” U.S. Patent US4777260, issued June, 1983.

    US4777260
    General ReferenceNot Available
    External Links
    ResourceLink
    KEGG DrugD00440
    KEGG CompoundC07270
    PubChem Compound3033637
    PubChem Substance46507554
    ChemSpider2298266
    Therapeutic Targets DatabaseDAP000339
    PharmGKBPA164752234
    Drug Product Database2246046
    RxListhttp://www.rxlist.com/cgi/generic/nizat.htm
    Drugs.comhttp://www.drugs.com/cdi/nizatidine.html
    WikipediaNizatidine
    ATC CodesA02BA04
    AHFS Codes
    • 56:28.12
    PDB EntriesNot Available
    FDA labelshow(380 KB)
    MSDSNot Available
    Interactions
    Drug Interactions
    Drug
    AtazanavirThis gastric pH modifier decreases the levels/effects of atazanavir
    CefditorenH2-Antagonists such as nizatidine may decrease the serum concentration of cefditoren. Cefditoren prescribing information recommends to avoid concomitant use with H2-antagonists (eg, famotidine, ranitidine) and antacids as well. Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of H2-antagonists can not be avoided.
    EnoxacinNizatidine may decrease the absorption of enoxacin.
    ItraconazoleThe H2-receptor antagonist, nizatidine, may decrease the absorption of itraconazole.
    KetoconazoleThe H2-receptor antagonist, nizatidine, may decrease the absorption of ketoconazole.
    Food Interactions
    • Avoid alcohol.
    • Avoid excessive quantities of coffee or tea (Caffeine).
    • Do not take Aluminum or magnesium antacids or supplements while on this medication.
    • May take Vitamin D.
    • No iron, zinc or fluoride within 2 hours of taking this medication.
    • Take without regard to meals.

    1. Histamine H2 receptor

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: antagonist

    Components

    Name UniProt ID Details
    Histamine H2 receptor P25021 Details

    References:

    1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
    2. Enriz RD, Jauregui EA: [Theoretical conformation study of tiotidine and nizatidine, two strong histamine H2-receptor antagonists] Acta Cient Venez. 1991;42(2):70-6. Pubmed
    3. Meredith CG, Speeg KV Jr, Schenker S: Nizatidine, a new histamine H2-receptor antagonist, and hepatic oxidative drug metabolism in the rat: a comparison with structurally related compounds. Toxicol Appl Pharmacol. 1985 Feb;77(2):315-24. Pubmed
    4. Lin TM, Evans DC, Warrick MW, Pioch RP: Actions of nizatidine, a selective histamine H2-receptor antagonist, on gastric acid secretion in dogs, rats and frogs. J Pharmacol Exp Ther. 1986 Nov;239(2):406-10. Pubmed
    5. Okabe S, Takeuchi K, Okada M, Kumadaki Y, Nakata M, Nakata H: [Effects of nizatidine, a new histamine H2-receptor antagonist, on gastric acid secretion and various gastric and duodenal lesions in rats: comparison with cimetidine] Nippon Yakurigaku Zasshi. 1989 Mar;93(3):133-44. Pubmed
    6. Kounenis G, Koutsoviti-Papadopoulou M, Elezoglou V: The excitatory effect of the new histamine H2-receptor antagonist nizatidine (LY 139037) on the guinea pig ileum. J Pharmacobiodyn. 1987 Nov;10(11):669-72. Pubmed

    1. Cholinesterase

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Cholinesterase P06276 Details

    References:

    1. Laine-Cessac P, Turcant A, Premel-Cabic A, Boyer J, Allain P: Inhibition of cholinesterases by histamine 2 receptor antagonist drugs. Res Commun Chem Pathol Pharmacol. 1993 Feb;79(2):185-93. Pubmed

    1. Multidrug resistance protein 1

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: substrate

    Components

    Name UniProt ID Details
    Multidrug resistance protein 1 P08183 Details

    References:

    1. Dahan A, Sabit H, Amidon GL: The H2 receptor antagonist nizatidine is a P-glycoprotein substrate: characterization of its intestinal epithelial cell efflux transport. AAPS J. 2009 Jun;11(2):205-13. Epub 2009 Mar 25. Pubmed

    Comments
    Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11