64490-92-2

• 常用中文名：托美丁钠(二水)
• 常用英文名：Tolmetin (sodium dihydrate)
• CAS号：64490-92-2
• 分子式：C₁₅H₁₈NNaO₅
• 分子量：315.30
• 相关类别： 研究领域 炎症/免疫
• 发布时间：2018-09-27 12:40:40
• 更新时间：2024-01-05 12:50:31
• Tolmetin sodium dihydrate 是一种非甾体抗炎剂,为非选择性的 COX 抑制剂。

名称

• 中文名: 托美丁钠(二水)
• 英文名: Tolmetin Sodium Salt Dihydrate
• 中文别名: 托美丁钠二水; 2-[1-甲基-5-(4-甲基苯甲酰)吡咯-2-基]乙酸钠(二水); 1-甲基-5-(P-甲苯酰基)吡咯-2-乙酸钠盐; 托美丁钠二水合物
• 英文别名: EINECS 252-687-3; sodium,2-[1-methyl-5-(4-methylbenzoyl)pyrrol-2-yl]acetate,dihydrate; 1H-Pyrrole-2-acetic acid, 1-methyl-5-(4-methylbenzoyl)-, sodium salt, hydrate (1:1:2); MFCD00079607; Tolmetin (sodium dihydrate)

物化性质

• 沸点: 483.2ºC at 760 mmHg
• 熔点: 155-157 (dec.)
• 分子式: C₁₅H₁₈NNaO₅
• 分子量: 315.30
• 闪点: 246ºC
• PSA: 80.59000
• LogP: 0.72830
• 外观性状: 结晶固体
• 储存条件: -20°C Freezer

生物活性

• 描述: Tolmetin sodium dihydrate 是一种非甾体抗炎剂,为非选择性的 COX 抑制剂。
• 相关类别:
  研究领域 >> 炎症/免疫
• 靶点:

  COX

• 体外研究: 托美汀钠二水合物是非甾体抗炎剂。托美汀(0-100μM)对成骨细胞生长没有影响[2]。托美汀(0.25mM)剂量不会减弱大鼠脑匀浆中的脂质过氧化。托美汀(0.25,0.5,0.75,1mM)显示出自由基清除特性,但在大鼠脑匀浆中没有产生超氧阴离子[3]。
• 体内研究: 托美汀(100mg/kg)引起胃损伤,并且在单剂量后4小时显示最大的溃疡形成作用,而在重复施用后3和14天后有效降低。托美汀产生明显的内皮损伤和炎症细胞浸润[1]。托美汀(5 mg/kg,腹腔注射,每天两次,连续5天)对大鼠的n NMDA受体结合没有影响[3]。
• 动物实验: 大鼠[1]适应2周后，将大鼠随机分到不同组，并给予非选择性COX抑制剂，氨甲喋呤（AMG）（50和150 mg / kg）和托美汀（30和100 mg / kg）。作为选择性COX-2抑制剂，塞来昔布（CXIB; 20和60mg / kg）。在使用前立即将化合物悬浮在1％羧甲基纤维素（CMC）中，并通过管饲法以10mL / kg体积给药。控制组在同一卷中接收CMC。将每组的大鼠分成3个亚组，每组至少10只动物。亚组用单剂量（急性治疗组）或每日两次给药3天和14天（慢性治疗组）。为确保所有组在相同的时间内给药，接受少于14天NSAID的患者将获得CMC，直至他们开始指定的治疗。在最后一次给药后4小时，通过颈脱位处死大鼠。立即取出胃，沿较小的曲率打开并轻轻冲洗[1]。
• 参考文献:

  [1]. Morini G, et al. Morphological features of rat gastric mucosa after acute and chronic treatment with amtolmetin guacyl: comparison with non-selective and COX-2-selective NSAIDs. Digestion. 2003;68(2-3):124-32. Epub 2003 Nov 7.

  [2]. Etcheverry SB, et al. Three new vanadyl(IV) complexes with non-steroidal anti-inflammatory drugs (Ibuprofen, Naproxen and Tolmetin). Bioactivity on osteoblast-like cells in culture. J Inorg Biochem. 2002 Jan 1;88(1):94-100.

  [3]. Dairam A, et al. Non-steroidal anti-inflammatory agents, tolmetin and sulindac, attenuate oxidative stress in rat brain homogenate and reduce quinolinic acid-induced neurodegeneration in rat hippocampal neurons. Metab Brain Dis. 2006 Sep;21(2-3):221-33.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : UX9280000 CHEMICAL NAME : 1H-Pyrrole-2-acetic acid, 1-methyl-5-(4-methylbenzoyl)-, sodium salt, dihydrate CAS REGISTRY NUMBER : 64490-92-2 LAST UPDATED : 199603 DATA ITEMS CITED : 15 MOLECULAR FORMULA : C15-H14-N-O3.Na.2H2-O MOLECULAR WEIGHT : 315.33 WISWESSER LINE NOTATION : T5NJ A1 BVR D1& E1VO &-NA- &QH 2 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 914 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #134763 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 612 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #134763 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1050 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Gastrointestinal - hypermotility, diarrhea REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 11,1099,1977 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >724 mg/kg TOXIC EFFECTS : Gastrointestinal - ulceration or bleeding from stomach Blood - changes in spleen REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 11,1099,1977 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 899 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #134763 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 550 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #134763 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 670 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Gastrointestinal - ulceration or bleeding from stomach REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 11,1099,1977 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >622 mg/kg TOXIC EFFECTS : Gastrointestinal - ulceration or bleeding from large intestine Blood - changes in spleen REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 11,1099,1977 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 9360 mg/kg/26W-I TOXIC EFFECTS : Gastrointestinal - other changes Endocrine - adrenal cortex hyperplasia Blood - changes in cell count (unspecified) REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 11,1117,1977 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 3720 mg/kg/31D-I TOXIC EFFECTS : Endocrine - changes in spleen weight Blood - pigmented or nucleated red blood cells Nutritional and Gross Metabolic - weight loss or decreased weight gain REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 11,1107,1977 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 43800 mg/kg/2Y-I TOXIC EFFECTS : Gastrointestinal - ulceration or bleeding from stomach Blood - normocytic anemia REFERENCE : YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 30,557,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 33306 mg/kg/78W-I TOXIC EFFECTS : Gastrointestinal - ulceration or bleeding from stomach Blood - normocytic anemia REFERENCE : YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 30,557,1979 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Primate - monkey DOSE/DURATION : 134 gm/kg/1Y-I TOXIC EFFECTS : Gastrointestinal - ulceration or bleeding from stomach Blood - normocytic anemia REFERENCE : YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 30,557,1979 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 163 mg/kg SEX/DURATION : female 6-18 day(s) after conception TOXIC EFFECTS : Reproductive - Specific Developmental Abnormalities - musculoskeletal system REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 8,158,1977 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 1300 mg/kg SEX/DURATION : female 6-18 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - abortion REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 8,158,1977

安全

• 符号: GHS07
• 信号词: Warning
• 危害声明: H302-H315
• 警示性声明: P301 + P312 + P330
• 危害码 (欧洲): Xn: Harmful;
• 风险声明 (欧洲): R22;R38
• 安全声明 (欧洲): S36
• 危险品运输编码: NONH for all modes of transport
• WGK德国: 3
• RTECS号: UX9280000