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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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Nizatidinesolution15 mg/mLoralAffordable Pharmaceuticals, LLC2009-12-18Not AvailableUs
Axidsolution15 mg/mLoralBraintree Laboratories, Inc.2005-06-30Not AvailableUs
Axidcapsule150 mgoralPendopharm Division Of De Pharmascience IncNot AvailableNot AvailableCanada
Axidcapsule300 mgoralPendopharm Division Of De Pharmascience IncNot AvailableNot AvailableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Nizatidinecapsule150 mgoralEon Labs, Inc.2002-07-05Not AvailableUs
Nizatidinecapsule300 mgoralEon Labs, Inc.2002-07-05Not AvailableUs
Nizatidinecapsule150 mgoralMylan Pharmaceuticals Inc.2011-05-04Not AvailableUs
Nizatidinecapsule300 mgoralMylan Pharmaceuticals Inc.2011-05-06Not AvailableUs
Nizatidinecapsule150 mgoralWatson Laboratories, Inc.2002-07-09Not AvailableUs
Nizatidinecapsule300 mgoralWatson Laboratories, Inc.2002-07-09Not AvailableUs
Nizatidinecapsule150 mgoralnizatidine2010-01-14Not AvailableUs
Nizatidinecapsule300 mgoralRebel Distributors Corp2002-07-09Not AvailableUs
Nizatidinecapsule150 mgoralRebel Distributors Corp2002-07-05Not AvailableUs
Nizatidinecapsule150 mgoralRebel Distributors Corp2002-07-09Not AvailableUs
Nizatidinecapsule150 mgoralH.J. Harkins Company, Inc.2002-07-09Not AvailableUs
Nizatidinecapsule150 mgoralDr Reddy's Laboratories Limited2005-09-15Not AvailableUs
Nizatidinecapsule300 mgoralDr Reddy's Laboratories Limited2005-09-15Not AvailableUs
Nizatidinecapsule150 mgoralProficient Rx LP2011-07-15Not AvailableUs
Nizatidinecapsule300 mgoralbryant ranch prepack2005-09-15Not AvailableUs
Nizatidinecapsule150 mgoralbryant ranch prepack2005-09-15Not AvailableUs
Nizatidinesolution15 mg/mLoralAmneal Pharmaceuticals2009-12-14Not AvailableUs
Nizatidinecapsule150 mgoralCarilion Materials Management2002-07-09Not AvailableUs
Nizatidinecapsule300 mgoralDispensing Solutions Inc.2009-01-22Not AvailableUs
Nizatidinecapsule150 mgoralGlenmark Generics Inc.,USA2011-07-15Not AvailableUs
Nizatidinecapsule300 mgoralGlenmark Generics Inc.,USA2011-07-15Not AvailableUs
Nizatidinecapsule150 mgoralPreferred Pharmaceuticals, Inc2012-03-29Not AvailableUs
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Axid Artablet, film coated75 mgoralWyeth Consumer Healthcare1996-05-09Not AvailableUs
International Brands
NameCompany
AcinonNot Available
TazacEli Lilly
Brand mixturesNot Available
SaltsNot 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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as 2,4-disubstituted thiazoles. These are compounds containing a thiazole ring substituted at the positions 2 and 3.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzoles
Sub ClassThiazoles
Direct Parent2,4-disubstituted thiazoles
Alternative Parents
Substituents
  • Aralkylamine
  • 2,4-disubstituted 1,3-thiazole
  • Heteroaromatic compound
  • Organic nitro compound
  • Tertiary aliphatic amine
  • Tertiary amine
  • Organic nitrite
  • C-nitro compound
  • Azacycle
  • Dialkylthioether
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Allyl-type 1,3-dipolar organic compound
  • Sulfenyl compound
  • Thioether
  • Organic oxoazanium
  • Hydrocarbon derivative
  • Organic salt
  • Organosulfur compound
  • Organonitrogen compound
  • Amine
  • Organic zwitterion
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
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
PropertyValueProbability
Human Intestinal Absorption+0.9572
Blood Brain Barrier+0.5
Caco-2 permeable-0.589
P-glycoprotein substrateSubstrate0.8357
P-glycoprotein inhibitor INon-inhibitor0.8947
P-glycoprotein inhibitor IINon-inhibitor0.8861
Renal organic cation transporterNon-inhibitor0.7832
CYP450 2C9 substrateNon-substrate0.8108
CYP450 2D6 substrateNon-substrate0.6721
CYP450 3A4 substrateNon-substrate0.5916
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 substrateNon-inhibitor0.9072
CYP450 2D6 substrateNon-inhibitor0.9231
CYP450 2C19 substrateNon-inhibitor0.9025
CYP450 3A4 substrateNon-inhibitor0.8508
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7826
Ames testNon AMES toxic0.6129
CarcinogenicityNon-carcinogens0.9182
BiodegradationNot ready biodegradable0.9295
Rat acute toxicity2.4350 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6244
hERG inhibition (predictor II)Non-inhibitor0.8734
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
Capsuleoral150 mg
Capsuleoral300 mg
Solutionoral15 mg/mL
Tablet, film coatedoral75 mg
Prices
Unit descriptionCostUnit
Axid 300 mg pulvule6.0USD each
Nizatidine 300 mg capsule4.97USD capsule
Axid 300 mg Capsule3.98USD capsule
Axid 150 mg pulvule3.62USD each
Nizatidine 150 mg capsule2.48USD capsule
Axid 150 mg Capsule2.06USD capsule
Apo-Nizatidine 300 mg Capsule0.96USD capsule
Novo-Nizatidine 300 mg Capsule0.96USD capsule
Pms-Nizatidine 300 mg Capsule0.96USD capsule
Axid 15 mg/ml Solution0.84USD ml
Nizatidine 15 mg/ml Solution0.76USD ml
Apo-Nizatidine 150 mg Capsule0.53USD capsule
Gen-Nizatidine 150 mg Capsule0.53USD capsule
Novo-Nizatidine 150 mg Capsule0.53USD capsule
Pms-Nizatidine 150 mg Capsule0.53USD capsule
Axid ar 75 mg tablet0.3USD tablet
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 Solubility0.0386 mg/mLALOGPS
logP0.7ALOGPS
logP0.76ChemAxon
logS-3.9ALOGPS
pKa (Strongest Basic)6.83ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area86.01 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity96.84 m3·mol-1ChemAxon
Polarizability35.49 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
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
ATC CodesA02BA04
AHFS Codes
  • 56:28.12
PDB EntriesNot Available
FDA labelDownload (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