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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
AcinonNot AvailableNot Available
AxidNot AvailableNot Available
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 KeySGXXNSQHWDMGGP-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
Not Available
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.

Targets

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

Enzymes

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

Transporters

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

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