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
Synonyms
  • Nizatidina
  • Nizatidine
  • Nizatidinum
External IDs
LY-139037
Product Images
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
AxidSolution15 mg/1mLOralPhysicians Total Care, Inc.2006-12-072009-06-30Us
AxidCapsule300 mg/1OralGlaxosmithkline Inc2007-03-012010-01-01Us
AxidCapsule300 mg/1OralPhysicians Total Care, Inc.2000-11-142011-05-31Us
AxidCapsule150 mg/1OralGlaxosmithkline Inc2007-03-012011-08-31Us
AxidSolution15 mg/1mLOralBraintree Laboratories2005-06-302013-12-09Us
AxidCapsule150 mg/1OralPhysicians Total Care, Inc.2000-11-142011-05-31Us
Nizatidine-150Capsule150 mgOralPro Doc Limitee2001-02-122010-07-13Canada
Nizatidine-300Capsule300 mgOralPro Doc Limitee2001-02-122010-07-13Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-nizatidineCapsule300 mgOralApotex Corporation1998-12-31Not applicableCanada
Apo-nizatidineCapsule150 mgOralApotex Corporation1998-12-31Not 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
NizatidineSolution15 mg/1mLOralAffordable Pharmaceuticals, LLC2009-12-182013-12-09Us
NizatidineCapsule300 mg/1OralDispensing Solutions, Inc.2009-01-22Not applicableUs
NizatidineCapsule150 mg/1Oralbryant ranch prepack2005-09-152018-06-05Us
NizatidineCapsule150 mg/1OralDr Reddy's Laboratories2005-09-15Not applicableUs
NizatidineCapsule300 mg/1OralMylan Pharmaceuticals2002-07-10Not applicableUs
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Axid ArTablet, film coated75 mg/1OralWyeth Consumer Healthcare Llc1996-05-092012-08-31Us
International/Other Brands
Acinon / Tazac (Eli Lilly)
Categories
UNII
P41PML4GHR
CAS number
76963-41-2
Weight
Average: 331.45
Monoisotopic: 331.113667284
Chemical Formula
C12H21N5O2S2
InChI Key
SGXXNSQHWDMGGP-UHFFFAOYSA-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
IUPAC Name
dimethyl[(4-{[(2-{[1-(methylamino)-2-nitroethenyl]amino}ethyl)sulfanyl]methyl}-1,3-thiazol-2-yl)methyl]amine
SMILES
CNC(NCCSCC1=CSC(CN(C)C)=N1)=C[N+]([O-])=O

Pharmacology

Indication

For the treatment of acid-reflux disorders (GERD), peptic ulcer disease, active benign gastric ulcer, and active duodenal ulcer.

Associated Conditions
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.

TargetActionsOrganism
AHistamine H2 receptor
antagonist
Human
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
PathwayCategory
Nizatidine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamine2,5-Dimethoxy-4-ethylamphetamine may decrease the sedative and stimulatory activities of Nizatidine.
2,5-Dimethoxy-4-ethylthioamphetamine2,5-Dimethoxy-4-ethylthioamphetamine may decrease the sedative and stimulatory activities of Nizatidine.
3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine may decrease the sedative and stimulatory activities of Nizatidine.
4-Bromo-2,5-dimethoxyamphetamine4-Bromo-2,5-dimethoxyamphetamine may decrease the sedative and stimulatory activities of Nizatidine.
AbemaciclibThe serum concentration of Nizatidine can be increased when it is combined with Abemaciclib.
AcetaminophenThe serum concentration of Nizatidine can be increased when it is combined with Acetaminophen.
AcipimoxThe risk or severity of myopathy, rhabdomyolysis, and myoglobinuria can be increased when Nizatidine is combined with Acipimox.
AfatinibThe serum concentration of Nizatidine can be increased when it is combined with Afatinib.
AlbendazoleThe serum concentration of Nizatidine can be increased when it is combined with Albendazole.
AldosteroneThe serum concentration of Nizatidine can be decreased when it is combined with Aldosterone.
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.

References

Synthesis Reference

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

US4777260
General References
Not Available
External Links
KEGG Drug
D00440
KEGG Compound
C07270
PubChem Compound
3033637
PubChem Substance
46507554
ChemSpider
4356
ChEBI
7601
ChEMBL
CHEMBL3183075
Therapeutic Targets Database
DAP000339
PharmGKB
PA164752234
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Nizatidine
ATC Codes
A02BA04 — Nizatidine
AHFS Codes
  • 56:28.12 — Histamine H2-antagonists
FDA label
Download (380 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceGastroparesis1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedTreatmentHealthy Volunteers2
3CompletedTreatmentGastro-esophageal Reflux Disease (GERD) / Heartburn1
4CompletedTreatmentSchizophrenic Disorders1
Not AvailableCompletedNot AvailableCommunity Acquired Pneumonia (CAP) / Gastro-esophageal Reflux Disease (GERD)1

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
  • Affordable Pharmaceuticals LLC
  • Amneal Pharmaceuticals
  • Apotex Inc.
  • Braintree Laboratories Inc.
  • Cardinal Health
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Doctor Reddys Laboratories Ltd.
  • Eon Labs
  • H.J. Harkins Co. Inc.
  • Lyne Laboratories Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Novopharm Ltd.
  • Par Pharmaceuticals
  • Patheon Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prescript Pharmaceuticals
  • Promex Medical Inc.
  • Rebel Distributors Corp.
  • Reliant Pharmaceuticals
  • Sandhills Packaging Inc.
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • Teva Pharmaceutical Industries Ltd.
  • Torpharm Inc.
  • UDL Laboratories
  • Vangard Labs Inc.
  • Watson Pharmaceuticals
  • Wyeth Pharmaceuticals
Dosage forms
FormRouteStrength
SolutionOral15 mg/1mL
Tablet, film coatedOral75 mg/1
CapsuleOral150 ug/1
CapsuleOral150 mg/1
CapsuleOral300 mg/1
CapsuleOral300 ug/1
CapsuleOral150 mg
CapsuleOral300 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
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6930119No2002-07-172022-07-17Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)130-132 °CPhysProp
water solubility10-33mg/mLNot Available
logP1.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0386 mg/mLALOGPS
logP0.7ALOGPS
logP0.77ChemAxon
logS-3.9ALOGPS
pKa (Strongest Basic)6.54ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area83.33 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity95.84 m3·mol-1ChemAxon
Polarizability35.54 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azoles
Sub Class
Thiazoles
Direct Parent
2,4-disubstituted thiazoles
Alternative Parents
Aralkylamines / Heteroaromatic compounds / Trialkylamines / C-nitro compounds / Sulfenyl compounds / Propargyl-type 1,3-dipolar organic compounds / Organic oxoazanium compounds / Dialkylthioethers / Dialkylamines / Azacyclic compounds
show 4 more
Substituents
2,4-disubstituted 1,3-thiazole / Aralkylamine / Heteroaromatic compound / Tertiary aliphatic amine / C-nitro compound / Tertiary amine / Organic nitro compound / Azacycle / Secondary amine / Dialkylthioether
show 17 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
C-nitro compound, tertiary amino compound, carboxamidine, 1,3-thiazole, organic sulfide (CHEBI:7601)

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 diff...
Gene Name
HRH2
Uniprot ID
P25021
Uniprot Name
Histamine H2 receptor
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
Uniprot Name
Cholinesterase
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
Uniprot Name
Multidrug resistance protein 1
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]

Drug created on June 13, 2005 07:24 / Updated on November 13, 2018 07:49