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ニザチジン
N-[2-(2-ジメチルアミノメチル-4-チアゾリルメチルチオ)エチル]-N'-メチル-2-ニトロビニリデンジアミン · ニザチジン · ドルセン · チザノン · アシノン · ニザチン · ニザノン · ニザトリック
識別子と物理属性
| CAS No. | 76963-41-2 |
|---|---|
| 分子式 | C12H21N5O2S2 |
| 平均分子量 | 331.5 g/mol |
| 単同位体質量 | 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 |
| 現地名 | ニザチジン |
化学・物理的性質
| XLogP | 1.6 |
|---|---|
| 極性表面積 | 140 |
| 水素結合供与体数 | 2 |
| 水素結合受容体数 | 8 |
| 回転可能結合数 | 9 |
| 重原子数 | 21 |
| 形式電荷 | 0 |
| 複雑度 | 349 |
| 物質分類 | Pharmaceutical |
| 臭い | Mild, sulfur-like odor |
| 味 | Bitter |
| Color/Form | Crystals from ethanol-ethyl acetateOff-white to buff crystalline solid |
| 溶解度 | 10-33mg/mLSoluble in water水に溶けにくく、メタノールに溶ける。21.4g/L(温度表記なし) |
| Human Drugs | Breast FeedingLactationAnti-Ulcer AgentsHistamine H2 AntagonistsGastrointestinal AgentsFDA approved drugs -> Active ingredient |
| 融点 | 130-132 °C130-1320C |
| Collision Cross Section | 178.1 Ų [M+Na]+ [CCS Type: DTBuffer gas: N2Ionization: ESI+Dataset: TOXCASTSource Identifier: DTXSID5023376] |
| 沸点 | 478.2±45.0 °C(Predicted) |
| 密度 | 1.249±0.06 g/cm3(Predicted) |
| 貯蔵条件 | Keep in dark place,Inert atmosphere,Room temperature |
| pKa（酸解離定数） | 2.1, 6.8(at 25℃) |
| 外観・状態 | Solid |
| 色 | オフホワイトからペールイエロー |
| 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 データベース | 76963-41-2(CAS DataBase Reference) |
化学的特性
White Crystalline Powder
安全性と法規制
| GHS 分類 | 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. |
|---|---|
| その他の安全情報 | IMAP assessments - 1,1-Ethenediamine, N-[2-[[[2-[(dimethylamino)methyl]-4-thiazolyl]methyl]thio]ethyl]-N'-methyl-2-nitro-: Environment tier I assessment |
| FDA 要件 | 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%) |
| 処分方法 | 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. |
| 相互作用 | 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 |
| 水環境危害等級（WGK） | 3 |
| RTECS 番号 | KM6565000 |
| 毒性 | LD50 in mice, rats (mg/kg): 265, >300 i.v.1685, 1680 orally (Pioch) |
| 税関コード | 29349990 |
| 危険文句（R） | 22 |
| 危険表示 | Xn |
| 安全措置（S） | 36 |
| 危険等級 | Acute Tox. 4 Oral |
| 貯蔵分類 | 11 - Combustible Solids |
| 有害物質データ | 76963-41-2(Hazardous Substances Data) |
用途
用途
ヒスタミンH2 受容体遮断剤 です。胃粘膜のヒスタミンH2受容体を遮断し、 胃酸分泌を抑制作用を示します。
説明
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.
使用
Nizatidine is used for treating stomach and duodenum ulcers and other conditions accompanied by elevated acidity of the gastrointestinal tract.
一般的な説明
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.