Nizatidine
axid · nizax · ze-101 · Nizaxi · ZL-101 · Acinon · gastrax · nizaxid
Identifiers & Physical Properties
| CAS No. | 76963-41-2 |
|---|---|
| Molecular formula | C12H21N5O2S2 |
| Average molar mass | 331.5 g/mol |
| Monoisotopic mass | 331.11366691 g/mol |
| SMILES | CNC(=C[N+](=O)[O-])NCCSCc1csc(CN(C)C)n1 |
| InChIKey | SGXXNSQHWDMGGP-UHFFFAOYSA-N |
| PubChem CID | 4513 |
| ChEMBL | CHEMBL3183075 |
| EC No. | 627-310-4 |
| DTXSID | DTXSID5023376 |
Chemical & Physical Properties
| XLogP | 1.6 |
|---|---|
| Topological polar surface area | 140 |
| Hydrogen bond donors | 2 |
| Hydrogen bond acceptors | 8 |
| Rotatable bonds | 9 |
| Heavy atoms | 21 |
| Formal charge | 0 |
| Complexity | 349 |
| Chemical classes | Pharmaceutical |
| Odor | Mild, sulfur-like odor |
| Taste | Bitter |
| Color/Form | Crystals from ethanol-ethyl acetateOff-white to buff crystalline solid |
| Solubility | 10-33mg/mLSoluble in waterSparingly soluble in water, soluble in methanol.21.4g/L(temperature not stated) |
| Human Drugs | Breast FeedingLactationAnti-Ulcer AgentsHistamine H2 AntagonistsGastrointestinal AgentsFDA approved drugs -> Active ingredient |
| Melting point | 130-132 °C130-1320C |
| Collision Cross Section | 178.1 Ų [M+Na]+ [CCS Type: DTBuffer gas: N2Ionization: ESI+Dataset: TOXCASTSource Identifier: DTXSID5023376] |
| Boiling point | 478.2±45.0 °C(Predicted) |
| Density | 1.249±0.06 g/cm3(Predicted) |
| Storage conditions | Keep in dark place,Inert atmosphere,Room temperature |
| pKa (acidity coefficient) | 2.1, 6.8(at 25℃) |
| Physical state | Solid |
| Color | Off-White to Pale Yellow |
| Merck | 14,6660 |
| 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 |
| InChIKey | SGXXNSQHWDMGGP-UHFFFAOYSA-N |
| SMILES | C(NCCSCC1=CSC(CN(C)C)=N1)(NC)=C[N+]([O-])=O |
| CAS DataBase Reference | 76963-41-2(CAS DataBase Reference) |
| FDA UNII | P41PML4GHR |
| ATC code | A02BA04 |
| UNSPSC Code | 41116107 |
| NACRES | NA.77 |
| Protein binding | 35% |
| Excreted unchanged in urine | 60% |
| Volume of distribution | 0.8-1.3(L/kg) |
| Biological half-life | 1-2 / 3.5-11 |
| GHS pictogram | GHS07 |
| Signal word | Warning |
| GHS hazard statements | H302 |
| GHS precautionary statements | P264-P270-P301+P312-P501 |
| Hazard symbols | Xn |
| Risk statements (R) | 22 |
| Safety statements (S) | 36 |
| Water hazard class (WGK) | 3 |
| RTECS number | KM6565000 |
| Customs code | 29349990 |
| Storage class | 11 - Combustible Solids |
| Hazard class | Acute Tox. 4 Oral |
| Hazardous substances data | 76963-41-2(Hazardous Substances Data) |
| Toxicity | LD50 in mice, rats (mg/kg): 265, >300 i.v.1685, 1680 orally (Pioch) |
Safety & Regulations
| GHS classification | WarningH302 (97.6%): Harmful if swallowed [Warning Acute toxicity, oral]P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 41 reports by companies from 2 notifications to the ECHA C&L Inventory. |
|---|---|
| Other safety information | IMAP assessments - 1,1-Ethenediamine, N-[2-[[[2-[(dimethylamino)methyl]-4-thiazolyl]methyl]thio]ethyl]-N'-methyl-2-nitro-: Environment tier I assessment |
| FDA requirements | Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended21 U.S.C. 321-392). |
| Hazard Classes and Categories | Acute Tox. 4 (97.6%) |
| Disposal methods | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. |
| Interactions | Concurrent use /of antacids/ with histamine H2-receptor antagonists in the treatment of peptic ulcer may be indicated for the relief of painhowever, simultaneous administration of antacids of medium to high potency (80 mmol to 150 mmol HCl) is not recommended since absorption of histamine H2-receptor antagonists may be decreasedpatients should be advised not to take any antacids within 1/2 to 1 hour of histamine H2-receptor antagonists. /Histamine H2-receptor antagonists/Concurrent use /of bone marrow depressants/ with H2-receptor antagonists may increase the risk of neutropenia or other blood dyscrasias. /Histamine H2-receptor antagonists/Histamine H2-receptor antagonists may increase gastrointestinal pHconcurrent administration of ketoconazole with histamine H2-receptor antagonists may result in a marked reduction in absorption of ketoconazolepatients should be advised to take histamine H2-receptor antagonists at least 2 hours after ketoconazole. /Histamine H2-receptor antagonists/Although a decrease in absorption is only reported in the literature for cimetidine and ranitidine, concurrent use with sucralfate may decrease the absorption of any H2-receptor antagonistpatients should be advised to take an H2-receptor antagonist 2 hours before sucralfate. /Histamine H2-receptor antagonists/No drug interactions were reported when nizatidine and theophylline, lidocaine, warfarin, chlordiazepoxide, diazepam, or lorazepam were used together. |
| Hepatotoxicity | Chronic therapy with nizatidine and other H2 blockers is associated with minor elevations in serum aminotransferase levels in 1% to 4% of patients, but similar rates have been reported in placebo recipients. The ALT elevations are usually asymptomatic and transient and may resolve without dose modification. Rare instances of clinically apparent liver injury have been reported in patients receiving nizatidine, but too few cases have been reported to characterize a typical time to onset or pattern of injury. More information is available on the hepatotoxicity of other H2 blockers such as ranitidine and cimetidine which have been implicated in causing clinically apparent liver injury in 1:20,000 to 1:100,000 users. The time to onset of H2 blocker induced liver injury tends to be short, between 1 and 6 weeks of starting. The typical pattern of serum enzyme elevations varies from hepatocellular to cholestatic, most cases being “mixed”. The injury can be severe, but is typically mild-to- moderate in severity and self-limited in course, resolving within 4 to 12 weeks of stopping. Immunoallergic features (rash, fever, eosinophilia) are uncommon, as is autoantibody formation. Liver biopsy histology often shows centrolobular (zone 3) necrosis with mixed cellular infiltrates and mild cholestasis. |
| Human Toxicity Excerpts | Nizatidine may inhibit alcohol dehydrogenase in the gastric mucosa and produce higher serum levels of alcohol, but this does not appear to be clinically significant. |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)NizatidinevLess-DILI-concern5Adverse reactionsDOI:10.1016/j.drudis.2016.02.015 |
| Non-Human Toxicity Excerpts | Studies in rats and mice with oral doses many times the recommended human dose showed no evidence of carcinogenicity.Studies in rats and rabbits with oral doses up to 300 and 55 times the human dose, respectively, have not shown that nizatidine impairs fertility.Rabbits treated with a dose equivalent to 300 times the human dose had abortions, a decreased number of live fetuses, and depressed fetal weights.Nizatidine is distributed into milk in rats, and growth depression has occurred in the offspring of lactating rats treated with the drug.For more Non-Human Toxicity Excerpts (Complete) data for NIZATIDINE (9 total), please visit the HSDB record page. |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during Lactation |
| USGS Health-Based Screening Levels for Evaluating Water-Quality | NizatidinePharmaceuticalSmith, C.D. and Nowell, L.H., 2024. Health-Based Screening Levels for evaluating water-quality data (3rd ed.). DOI:10.5066/F71C1TWP |
| Water hazard class (WGK) | 3 |
| RTECS number | KM6565000 |
| Customs code | 29349990 |
| Toxicity | LD50 in mice, rats (mg/kg): 265, >300 i.v.1685, 1680 orally (Pioch) |
| Risk statements (R) | 22 |
| Signal word | Warning |
| GHS pictogram | GHS07 |
| Hazard symbols | Xn |
| Safety statements (S) | 36 |
| Storage class | 11 - Combustible Solids |
| GHS hazard statements | H302 |
| Hazard class | Acute Tox. 4 Oral |
| GHS precautionary statements | P264-P270-P301+P312-P501 |
| Hazardous substances data | 76963-41-2(Hazardous Substances Data) |
Applications & Uses
Uses
The value of nizatidine in the treatment of peptic ulcer disease is comparable with that of ranitidine and cimetidine. 1 or 2 times daily dosing can typically cure duodenal ulcer within 8 weeks; a single dose administration daily can prevent recurrence (Bianchi-Porro and Keohane, 1987; Stern, 1988). The efficacy of nizatidine in the treatment of stomach ulcers is similar as that of other H2-blockers but with little information available. For reflux esophagitis, Zollinger-Ellison syndrome and other kinds of peptic ulcer diseases, it is expected to generate a equal effect as ranitidine but this still needs clinical studies.
Uses
It is a kind of H2 receptor antagonists. It can be used for the prevention of active duodenal ulcer, benign gastric ulcer and prevention of recurrence after the healing of the active duodenal ulcer.
Description
Nizatidine is the fifth H2-antagonist introduced to the world market as an antiulcer agent. It is reported to be effective in the treatment of both duodenal and gastric ulcers or the prevention of their recurrences. Given once-daily, nizatidine’s bioavailability is not diminished by the concurrent administration of an antacid.
Uses
Histamine H2-receptor antagonist related to Ranitidine (R120000). Antiulcerative.
Uses
immune suppressant, antineoplastic, antiviral
Uses
For the treatment of acid-reflux disorders (GERD), peptic ulcer disease, active benign gastric ulcer, and active duodenal ulcer.
Uses
Nizatidine is used for treating stomach and duodenum ulcers and other conditions accompanied by elevated acidity of the gastrointestinal tract.
General Description
Nizatidine, N-[2-[[[2-(dimethylamino)methyl]-4-thiazolyl]methyl]thio]-ethyl]-N'-methyl-2-nitro-1,1-ethenediamine (Axid), is an off-white to buff crystallinesolid that is soluble in water, alcohol, and chloroform. It isa thaizole derivative of raniditine and has pKas of 2.1 (side chain) and 6.8 (dimethylamino). Nizatidine’s mechanism ofaction is similar to other H2-antagonists, as is its receptor selectivity.It is more potent than cimetidine.Nizatidine has excellent oral bioavailability (＞90%).The effects of antacids or food on its bioavailability arenot clinically significant. The elimination half-life is 1 to2 hours. It is excreted primarily in the urine (90%) andmostly as unchanged drug (60%). Metabolites include nizatidinesulfoxide (6%), N-desmethylnizatidine (7%), andnizatidine N-oxide (dimethylaminomethyl function).Nizatidine has no demonstrable antiandrogenic action, effectson other hormones, or inhibitory effects on cytochromeisozymes involved in the metabolism of other drugs.