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| 中文名 | S-MTC |
|---|---|
| 英文名 | s-methyl-l-thiocitrulline |
| 英文别名 |
s-methylthiocitrulline
S-Me-TC,SMTC L-Thiocitrulline2HCl S-MTC |
| 描述 | S-MTC 是一种选择性的 I 型一氧化氮合酶 (NOS) 抑制剂。 |
|---|---|
| 相关类别 | |
| 靶点 |
NOS[1] |
| 体外研究 | 在不存在Aβ1-42的情况下,S-MTC(10或100μM)减少细胞NO释放。在100μM时,S-MTC降低细胞活力。与对照相比,S-MTC(100μM)显着降低亚硝酸盐产量(11.2±1.1μM)(无NOS抑制剂暴露; 19.6±1.2μM)。 Aβ1-42和L-NOARG(100μM)或Aβ1-42和S-MTC(100μM)处理后的亚硝酸盐产量显着低于单独的Aβ1-42(分别为33.5±2.0和34.5±1.6μM)。当在Aβ1-42在1小时时间点施用后,与单独的Aβ1-42处理(38.3±2.7μM)相比,S-MTC(100μM)能够显着减少亚硝酸盐产生(25.2±1.1μM)。 S-MTC(100μM)浓度降低MTT(对照的87±1％)和NR(分别为对照的80±1％)水平。共同施用S-MTC(100μM)和Aβ1-42显着逆转单独的Aβ1-42的作用(72±2％对比对照的61±2％)[1]。 |
| 体内研究 | S-MTC(S-甲基-L-硫代瓜氨酸)是选择性神经元NOS抑制剂。在用S-MTC(icv)预处理后,HBO2诱导的抗伤害感受被显着拮抗。在实验＃2中,用盐酸纳曲酮(NTX)(3.0mg/kg,ip),L-NAME(1.0μg/小鼠,icv),S-MTC(1.0μg/小鼠,icv)预处理不同组的小鼠或在HBO2处理之前15-30分钟,N5-(1-亚氨基乙基)-L-鸟氨酸(L-NIO)(3.0mg/kg,sc)。在HBO2治疗后90分钟评估的抗伤害感受效果被NTX和L-NAME完全消除,S-MTC对抗三分之二并且在很大程度上不受L-NIO的影响(F = 25.57,p <0.0001)[2]。在0.3mg/kg的剂量下,S-MTC(SMTC)引起平均血压(BP)升高。剂量为1.0,3.0和10 mg/kg时,S-MTC导致所有三个血管床的心率下降,血压升高和血管收缩[3]。 |
| 细胞实验 | 从Spargue-Dawley大鼠获得的E15至E18胚胎制备混合的皮质胶质细胞和神经元培养的细胞。在接种后第7天，除去培养基并在Aβ1-42（1,5,10或20μM），Aβ42-1或过氧亚硝酸盐（100或200μM）存在下用新制备的培养基替换。含或不含NG-硝基-L-精氨酸（L-NOARG，10或100μM），S-MTC（10或100μM），N-亚氨基乙基-L-赖氨酸（10或100μM），N-（3） - （氨基甲基）苄基）乙脒（1400W，1或5μM），2-（4-羧基苯基）-4,4,5,5-四甲基咪唑啉-1-氧基-3-氧化物（羧基-PTIO，10或100μM） ）或单独或组合的6-羟基-2,5,7,8-四甲基色满-2-羧酸（10或100μM）。然后将培养的细胞温育20小时。对于时程研究，用所述含有Aβ1-42（10μM）的培养基预处理培养的细胞。 L-NIL（100μM），L-NOARG（100μM），1400W（5μM），S-MTC（100μM），羧基-PTIO（100μM）或Trolox（100μM）以1,4给药，8小时后。在Aβ1-42给药后20小时进行评估。通过使用MTT和中性红比色测定评估培养细胞的活力。通过使用微量板读数器，MTT降低和NR摄取分别在570和540nm处定量[1]。 |
| 动物实验 | 小鼠[2]使用重18-22g的雄性NIH Swiss小鼠。施用S-MTC（1.0μg/小鼠）icv（15分钟预处理时间）。在一组实验（＃1，＃2和＃3）中，阿片样物质拮抗剂和NOS抑制剂在60分钟HBO2治疗前15-30分钟给药（在抗伤害性测试前180分钟）。在另一个实验（＃4）中，在60分钟HBO2治疗停止后60分钟（抗伤害性测试前15-30分钟）给予阿片类拮抗剂和NOS-抑制剂预处理。对于ip或sc预处理，注射体积为0.1mL / 10g体重，对照动物仅接受ip或sc注射载体（无菌盐水）。对于icv预处理，显微注射的体积为每只小鼠5.0μL，对照动物仅接受icv显微注射载体（无菌盐水）。大鼠[3]使用雄性Sprague-Dawley大鼠（350-450g）。在导管插入后第2天（第1天），动物（n = 7）接受静脉注射（0.1mL）盐水（载体）和0.3和3mg / kg S-MTC（n = 4）或0.1， 1和10mg / kg S-MTC（n = 3）。在第3天，切换剂量方案以确保每只动物已接受所有剂量的S-MTC。在每一天，药物以递增的剂量顺序给予，并且在两次剂量之间允许至少60分钟。允许间隔的第二天（第2天）洗去任何药物作用。 |
| 参考文献 |
| 密度 | 1.35 g/cm3 |
|---|---|
| 沸点 | 405ºC at 760 mmHg |
| 熔点 | 60ºC |
| 分子式 | C7H15N3O2S |
| 分子量 | 205.28 |
| 闪点 | 198.7ºC |
| PSA | 161.80000 |
| LogP | 1.34770 |
| 外观性状 | 灰白色粉末/白色固体 |
| 折射率 | 1.572 |
| 储存条件 | 2-8℃ |
Synonym:None Known Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS
Risk Phrases: None Listed. Section 3 - HAZARDS IDENTIFICATION EMERGENCY OVERVIEW
The toxicological properties of this material have not been fully investigated. Potential Health Effects Eye: May cause eye irritation. Skin: May cause skin irritation. May be harmful if absorbed through the skin. Ingestion: May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated. May be harmful if swallowed. Inhalation: May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated. May be harmful if inhaled. Chronic: No information found. Section 4 - FIRST AID MEASURES Eyes: In case of contact, immediately flush eyes with plenty of water for at least 15 minutes. Get medical aid. Skin: In case of contact, flush skin with plenty of water. Remove contaminated clothing and shoes. Get medical aid if irritation develops and persists. Wash clothing before reuse. Ingestion: If swallowed, do not induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an unconscious person. Get medical aid. Inhalation: If inhaled, remove to fresh air. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid. Notes to Physician: Treat symptomatically and supportively. Section 5 - FIRE FIGHTING MEASURES General Information: As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion. Extinguishing Media: Use water spray, dry chemical, carbon dioxide, or chemical foam. Section 6 - ACCIDENTAL RELEASE MEASURES General Information: Use proper personal protective equipment as indicated in Section 8. Spills/Leaks: Vacuum or sweep up material and place into a suitable disposal container. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions. Provide ventilation. Section 7 - HANDLING and STORAGE Handling: Wash thoroughly after handling. Use with adequate ventilation. Minimize dust generation and accumulation. Avoid breathing dust, vapor, mist, or gas. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation. Storage: Store in a tightly closed container. Keep refrigerated. (Store below 4C/39F.) Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION Engineering Controls: Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low. Exposure Limits CAS# 156719-41-4: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166. Skin: Wear appropriate protective gloves to prevent skin exposure. Clothing: Wear appropriate protective clothing to prevent skin exposure. Respirators: Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced. Section 9 - PHYSICAL AND CHEMICAL PROPERTIES Physical State: Powder Color: white - off-white Odor: odorless pH: Not available. Vapor Pressure: Not available. Viscosity: Not available. Boiling Point: Not available. Freezing/Melting Point: 60 deg C Autoignition Temperature: Not available. Flash Point: Not available. Explosion Limits, lower: Not available. Explosion Limits, upper: Not available. Decomposition Temperature: Solubility in water: Soluble. Specific Gravity/Density: Molecular Formula: C6H13N3O2S.2HCl Molecular Weight: 264.3 Section 10 - STABILITY AND REACTIVITY Chemical Stability: Stable. Conditions to Avoid: Dust generation, moisture, excess heat. Incompatibilities with Other Materials: Strong oxidizing agents. Hazardous Decomposition Products: Nitrogen oxides, carbon monoxide, oxides of sulfur, carbon dioxide. Hazardous Polymerization: Will not occur. Section 11 - TOXICOLOGICAL INFORMATION RTECS#: CAS# 156719-41-4 unlisted. LD50/LC50: Not available. Carcinogenicity: L-Thiocitrulline dihydrochloride - Not listed by ACGIH, IARC, or NTP. Section 12 - ECOLOGICAL INFORMATION Section 13 - DISPOSAL CONSIDERATIONS Dispose of in a manner consistent with federal, state, and local regulations. Section 14 - TRANSPORT INFORMATION IATA Not regulated as a hazardous material. IMO Not regulated as a hazardous material. RID/ADR Not regulated as a hazardous material. Section 15 - REGULATORY INFORMATION European/International Regulations European Labeling in Accordance with EC Directives Hazard Symbols: Not available. Risk Phrases: Safety Phrases: S 24/25 Avoid contact with skin and eyes. WGK (Water Danger/Protection) CAS# 156719-41-4: No information available. Canada None of the chemicals in this product are listed on the DSL/NDSL list. CAS# 156719-41-4 is not listed on Canada's Ingredient Disclosure List. US FEDERAL TSCA CAS# 156719-41-4 is not listed on the TSCA inventory. It is for research and development use only. SECTION 16 - ADDITIONAL INFORMATION N/A |