Banner
targets (1) transporters (1)
for drugs
Identification
Name Nizatidine
Accession Number DB00585 (APRD00706)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Acinon
  • Antizid
  • Axid
  • Axid Ar
  • Calmaxid
  • Cronizat
  • Distaxid
  • Galitidin
  • Gastrax
  • Naxidine
  • Niatidine
  • Nizatidina [Spanish]
  • Nizatidine [Usan:Ban:Inn:Jan]
  • Nizatidinum [Latin]
  • Nizax
  • Nizaxid
  • Panaxid
  • Splendil Er
  • Tazac
  • Ulcosol
  • Ulxid
  • Zanizal
  • Zinga
Brand name mixtures Not Available
Categories
  • Anti-Ulcer Agents
  • Histamine H2 Antagonists
CAS number 76963-41-2
Weight Average: 331.457
Monoisotopic: 331.113666321
Chemical Formula C12H21N5O2S2
InChI Key InChIKey=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+
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Thiazoles
Substructures
  • Ethers
  • Oxoazaniums
  • Nitro compounds
  • Aliphatic and Aryl Amines
  • Thiazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Imines
Pharmacology
Indication For the treatment of acid-reflux disorders (GERD), peptic ulcer disease, active benign gastric ulcer, and active duodenal ulcer.
Pharmacodynamics Nizatidine 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 action Nizatidine 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.
Absorption Rapid (bioavailability of nizatidine exceeds 70%)
Volume of distribution
  • 0.8 to 1.5 L/kg
Protein binding 35%
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).
Route of elimination Not Available
Half life 1-2 hours
Clearance
  • 40-60 L/h
  • 7 – 14 L/h [functionally anephric patients]
Toxicity Oral, 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
Pathway Name SMPDB ID
Smp00233 Nizatidine Pathway SMP00233
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
Form Route Strength
Capsule Oral
Prices
Unit description Cost Unit
Axid 300 mg pulvule 6.0 USD each
Nizatidine 300 mg capsule 4.97 USD capsule
Axid 300 mg Capsule 3.98 USD capsule
Axid 150 mg pulvule 3.62 USD each
Nizatidine 150 mg capsule 2.48 USD capsule
Axid 150 mg Capsule 2.06 USD capsule
Apo-Nizatidine 300 mg Capsule 0.96 USD capsule
Novo-Nizatidine 300 mg Capsule 0.96 USD capsule
Pms-Nizatidine 300 mg Capsule 0.96 USD capsule
Axid 15 mg/ml Solution 0.84 USD ml
Nizatidine 15 mg/ml Solution 0.76 USD ml
Apo-Nizatidine 150 mg Capsule 0.53 USD capsule
Gen-Nizatidine 150 mg Capsule 0.53 USD capsule
Novo-Nizatidine 150 mg Capsule 0.53 USD capsule
Pms-Nizatidine 150 mg Capsule 0.53 USD capsule
Axid ar 75 mg tablet 0.3 USD tablet
Patents
Country Patent Number Approved Expires
United States 6930119 2002-07-17 2022-07-17
Properties
State solid
Melting point 203 oC
Experimental Properties
Property Value Source
water solubility 10-33mg/mL PhysProp
logP 1.1 PhysProp
Predicted Properties
Property Value Source
water solubility 3.86e-02 g/l ALOGPS
logP 0.70 ALOGPS
logP 0.76 ChemAxon Molconvert
logS -3.93 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 6 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 86.01 ChemAxon Molconvert
rotatable bond count 10 ChemAxon Molconvert
refractivity 96.84 ChemAxon Molconvert
polarizability 35.48 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00440 Link_out
KEGG Compound C07270 Link_out
PubChem Compound 3033637 Link_out
PubChem Substance 46507554 Link_out
ChemSpider 2298266 Link_out
Therapeutic Targets Database DAP000339 Link_out
PharmGKB PA450646 Link_out
Drug Product Database 2246046 Link_out
RxList http://www.rxlist.com/cgi/generic/nizat.htm Link_out
Drugs.com http://www.drugs.com/cdi/nizatidine.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Nizatidine Link_out
ATC Codes
  • A02BA04
AHFS Codes
  • 56:28.12
PDB Entries Not Available
FDA label show (380.1 KB)
MSDS Not Available
Interactions
Drug Interactions Not Available
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

Pharmacological action: yes
Actions: antagonist

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) signaling pathway

Organism class: human
UniProt ID: P25021 Link_out
Gene: HRH2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Transporters

1. Multidrug resistance protein 1

Actions: substrate

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 November 10, 2010 13:40

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.