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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
Acinon
Axid
Nizatidina
Nizatidine
Nizatidinum
External Identifiers Not Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Axidcapsule300 mgoralPendopharm Division Of De Pharmascience Inc1988-12-31Not applicableCanada
Axidcapsule150 mgoralPendopharm Division Of De Pharmascience Inc1988-12-31Not applicableCanada
Dom-nizatidine 150mg Capsulescapsule150 mgoralDominion Pharmacal2001-10-31Not applicableCanada
Gen-nizatidinecapsule300 mgoralGenpharm Ulc2002-07-122010-08-04Canada
Gen-nizatidinecapsule150 mgoralGenpharm Ulc2002-07-122010-08-04Canada
Nizatidine-150capsule150 mgoralPro Doc Limitee2001-02-122010-07-13Canada
Nizatidine-300capsule300 mgoralPro Doc Limitee2001-02-122010-07-13Canada
Novo-nizatidinecapsule300 mgoralNovopharm Limited1999-07-23Not applicableCanada
Novo-nizatidinecapsule150 mgoralNovopharm Limited1999-07-23Not applicableCanada
Nu-nizatidinecapsule300 mgoralNu Pharm IncNot applicableNot applicableCanada
Nu-nizatidinecapsule150 mgoralNu Pharm IncNot applicableNot applicableCanada
PHL-nizatidinecapsule300 mgoralPharmel Inc1999-03-01Not applicableCanada
PHL-nizatidinecapsule150 mgoralPharmel Inc1999-03-01Not applicableCanada
PMS-nizatidinecapsule300 mgoralPharmascience Inc1998-04-28Not applicableCanada
PMS-nizatidine 150mg Capsulescapsule150 mgoralPharmascience Inc1998-04-28Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-nizatidinecapsule150 mgoralApotex Inc1998-12-31Not applicableCanada
Apo-nizatidinecapsule300 mgoralApotex Inc1998-12-31Not applicableCanada
Nizatidinecapsule150 mg/1oralEon Labs, Inc.2002-07-052016-04-23Us
Nizatidinecapsule150 mg/1oralbryant ranch prepack2005-09-152016-04-05Us
Nizatidinecapsule300 mg/1oralbryant ranch prepack2005-09-152016-04-05Us
Nizatidinecapsule150 mg/1oralRebel Distributors Corp2002-07-052016-04-05Us
Nizatidinecapsule150 mg/1oralPreferred Pharmaceuticals, Inc2012-03-292016-04-05Us
Nizatidinecapsule150 mg/1oralProficient Rx LP2011-07-152016-04-05Us
Nizatidinecapsule300 mg/1oralRebel Distributors Corp2002-07-092016-04-05Us
Nizatidinecapsule150 mg/1oralPreferred Pharmaceuticals Inc.2015-08-282016-04-05Us
Nizatidinecapsule150 mg/1oralLake Erie Medical DBA Quality Care Products LLC2002-07-092016-04-05Us
Nizatidinecapsule150 mg/1oralnizatidine2010-01-142016-04-05Us
Nizatidinecapsule300 mg/1oralGlenmark Generics Inc.,USA2011-07-152016-04-05Us
Nizatidinecapsule300 mg/1oralDr Reddy's Laboratories Limited2005-09-152016-04-05Us
Nizatidinecapsule300 mg/1oralWatson Laboratories, Inc.2002-07-092016-04-23Us
Nizatidinecapsule150 mg/1oralGlenmark Generics Inc.,USA2011-07-152016-04-05Us
Nizatidinecapsule150 mg/1oralDr Reddy's Laboratories Limited2005-09-152016-04-05Us
Nizatidinecapsule150 mg/1oralWatson Laboratories, Inc.2002-07-092016-04-23Us
Nizatidinecapsule300 mg/1oralDispensing Solutions Inc.2009-01-222016-04-05Us
Nizatidinecapsule150 mg/1oralH.J. Harkins Company, Inc.2002-07-092016-04-05Us
Nizatidinecapsule300 mg/1oralMylan Pharmaceuticals Inc.2011-05-062016-04-23Us
Nizatidinecapsule150 mg/1oralMedsource Pharmaceuticals2011-07-152016-04-05Us
Nizatidinecapsule150 mg/1oralMylan Pharmaceuticals Inc.2011-05-042016-04-23Us
Nizatidinecapsule150 mg/1oralCarilion Materials Management2002-07-092016-04-05Us
Nizatidinecapsule150 mg/1oralRebel Distributors Corp2002-07-092016-04-05Us
Nizatidinecapsule300 mg/1oralEon Labs, Inc.2002-07-052016-04-23Us
Nizatidinesolution15 mg/mLoralAmneal Pharmaceuticals2009-12-142016-04-05Us
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Axid Artablet, film coated75 mg/1oralWyeth Consumer Healthcare1996-05-092016-04-23Us
International Brands
NameCompany
AcinonNot Available
TazacEli Lilly
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIP41PML4GHR
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
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.
Related Articles
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 inhibitorNon-inhibitor0.9072
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
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
Capsuleoral300 mg
Tablet, film coatedoral75 mg/1
Capsuleoral150 mg
Capsuleoral150 mg/1
Capsuleoral300 mg/1
Solutionoral15 mg/mL
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
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6930119 No2002-07-172022-07-17Us
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 ReferencesNot Available
External Links
ATC CodesA02BA04
AHFS Codes
  • 56:28.12
PDB EntriesNot Available
FDA labelDownload (380 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AtazanavirThe serum concentration of Atazanavir can be decreased when it is combined with Nizatidine.
BosutinibThe serum concentration of Bosutinib can be decreased when it is combined with Nizatidine.
CefditorenThe serum concentration of Cefditoren can be decreased when it is combined with Nizatidine.
CefpodoximeNizatidine can cause a decrease in the absorption of Cefpodoxime resulting in a reduced serum concentration and potentially a decrease in efficacy.
CefuroximeNizatidine can cause a decrease in the absorption of Cefuroxime resulting in a reduced serum concentration and potentially a decrease in efficacy.
CysteamineThe therapeutic efficacy of Cysteamine can be decreased when used in combination with Nizatidine.
DabrafenibThe serum concentration of Dabrafenib can be decreased when it is combined with Nizatidine.
DasatinibNizatidine can cause a decrease in the absorption of Dasatinib resulting in a reduced serum concentration and potentially a decrease in efficacy.
DelavirdineThe serum concentration of Delavirdine can be decreased when it is combined with Nizatidine.
DexmethylphenidateNizatidine can cause an increase in the absorption of Dexmethylphenidate resulting in an increased serum concentration and potentially a worsening of adverse effects.
ErlotinibThe serum concentration of Erlotinib can be decreased when it is combined with Nizatidine.
FosamprenavirThe serum concentration of Fosamprenavir can be decreased when it is combined with Nizatidine.
GefitinibThe serum concentration of Gefitinib can be decreased when it is combined with Nizatidine.
IndinavirThe serum concentration of Indinavir can be decreased when it is combined with Nizatidine.
Iron DextranNizatidine can cause a decrease in the absorption of Iron Dextran resulting in a reduced serum concentration and potentially a decrease in efficacy.
ItraconazoleThe serum concentration of Itraconazole can be decreased when it is combined with Nizatidine.
KetoconazoleThe serum concentration of Ketoconazole can be decreased when it is combined with Nizatidine.
LedipasvirThe serum concentration of Ledipasvir can be decreased when it is combined with Nizatidine.
MesalazineThe therapeutic efficacy of Mesalazine can be decreased when used in combination with Nizatidine.
MethylphenidateNizatidine can cause an increase in the absorption of Methylphenidate resulting in an increased serum concentration and potentially a worsening of adverse effects.
NelfinavirThe serum concentration of Nelfinavir can be decreased when it is combined with Nizatidine.
NilotinibThe serum concentration of Nilotinib can be decreased when it is combined with Nizatidine.
PazopanibThe serum concentration of Pazopanib can be decreased when it is combined with Nizatidine.
PosaconazoleThe serum concentration of Posaconazole can be decreased when it is combined with Nizatidine.
RilpivirineThe serum concentration of Rilpivirine can be decreased when it is combined with Nizatidine.
RisedronateThe serum concentration of Risedronate can be increased when it is combined with Nizatidine.
SaquinavirThe serum concentration of Saquinavir can be increased when it is combined with Nizatidine.
VareniclineThe serum concentration of Varenicline can be increased when it is combined with Nizatidine.
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

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
antagonist
General Function:
Histamine receptor activity
Specific Function:
The H2 subclass of histamine receptors mediates gastric acid secretion. Also appears to regulate gastrointestinal motility and intestinal secretion. Possible role in regulating cell growth and differentiation. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and, through a separate G protein-dependent mechanism, the phosphoinositide/protein kinase (PKC) si...
Gene Name:
HRH2
Uniprot ID:
P25021
Molecular Weight:
40097.65 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  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:1843561 ]
  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:2858133 ]
  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:2877081 ]
  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]. Nihon Yakurigaku Zasshi. 1989 Mar;93(3):133-44. [PubMed:2567267 ]
  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:2895808 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Identical protein binding
Specific Function:
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name:
BCHE
Uniprot ID:
P06276
Molecular Weight:
68417.575 Da
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:8095733 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
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. doi: 10.1208/s12248-009-9092-5. Epub 2009 Mar 25. [PubMed:19319690 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on May 06, 2016 02:27