92-13-7

• 常用中文名：毛果芸香碱
• 常用英文名：Pilocarpine
• CAS号：92-13-7
• 分子式：C₁₁H₁₆N₂O₂
• 分子量：208.257
• 相关类别： 医药中间体 杂环化合物 嘧啶类化合物 尿(脲)嘧啶
• 发布时间：2018-05-29 08:00:00
• 更新时间：2024-01-01 22:54:57
• 匹罗卡品是一种选择性M3型毒蕈碱乙酰胆碱受体(M3毒蕈碱受体)激动剂。

名称

• 中文名: 匹罗卡品
• 英文名: (+)-pilocarpine
• 中文别名: 毛果云香碱; 毛果芸香碱
• 英文别名: ocusertp20; PILOCARPINE; pilokarpol; 3-ethyl-4-((1-methyl-1H-imidazol-5-yl)methyl)dihydro-2(3H)-furanone; Pilocarpol; 2(3H)-Furanone, 3-ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl)methyl]-; EINECS 202-128-4; 3-Ethyl-4-[(1-methyl-1H-imidazol-5-yl)methyl]dihydro-2(3H)-furanone; Pilocarpin; Syncarpine; Pilokarpin; Ocucarpine; Ocusert; MFCD00153042; actone

物化性质

• 密度: 1.2±0.1 g/cm3
• 沸点: 431.8±18.0 °C at 760 mmHg
• 熔点: 34℃
• 分子式: C₁₁H₁₆N₂O₂
• 分子量: 208.257
• 闪点: 215.0±21.2 °C
• 精确质量: 208.121185
• PSA: 44.12000
• LogP: -0.09
• 外观性状: 油状液体或结晶
• 蒸汽压: 0.0±1.0 mmHg at 25°C
• 折射率: 1.585
• 储存条件: -20°C， 惰性气体保存

生物活性

• 描述: 匹罗卡品是一种选择性M3型毒蕈碱乙酰胆碱受体(M3毒蕈碱受体)激动剂。
• 相关类别:
  信号通路 >> 神经信号通路 >> mAChR
  信号通路 >> G 蛋白偶联受体/G 蛋白 >> 由mAChR
  研究领域 >> 神经疾病
• 靶点:

  M3 muscarinic receptor[1]

• 体外研究: 为了评价匹罗卡品的细胞毒性,分别用光学显微镜和MTT法检测人角膜基质细胞(HCS)的形态和活性。形态学观察表明,暴露于浓度为0.625至20 g/L毛果芸香碱的HCS细胞表现出剂量和时间依赖性增殖迟缓和形态学异常,如细胞收缩、细胞质空泡化、脱离培养基质,最终死亡,而暴露于浓度低于0.625g/L的匹罗卡品组与对照组之间没有观察到明显差异。MTT试验结果表明,毛果芸香碱浓度高于0.625g/L时,HCS细胞的细胞活力随时间和浓度的增加而降低(P<0.01或0.05),而毛果芸香碱浓度低于0.625 g/L的HCS细胞与对照组相比无显著差异[2]。部分毒蕈碱激动剂匹罗卡品在用苯乙肾上腺素(10至200 nM)收缩的大鼠尾动脉孤立段中引起浓度依赖性舒张,EC50为2.4 mM[3]。
• 体内研究: 研究了匹罗卡品诱导的对照大鼠(CN)和运动大鼠(EX)的唾液分泌。毛果芸香碱在EX大鼠中诱导的唾液量显著高于CN大鼠(P<0.01)。相反,EX大鼠唾液中的钠离子浓度显著低于CN大鼠(P<0.05)[1]。
• 细胞实验: MTT法测定细胞活力。简而言之，将HCS细胞接种到密度为1×104个细胞/100µL/孔的96孔培养板（Nunc）中，并进行培养和处理。每隔4h，将含有毛果芸香碱（0.625至20 g/L）的培养基完全替换为含有1.0 g/L MTT的100µL无血清DMEM/F12培养基，并将细胞在37°C的黑暗中培养4h。小心丢弃含MTT的培养基后，添加150µL二甲基亚砜以在37°C下在黑暗中溶解产生的福尔马赞晶体15分钟，并使用Multiskan GO微孔板读取器测量490 nm处的吸光度[2]。
• 动物实验: 大鼠[1]将10周龄雄性Wistar大鼠分为两组，运动组（EX，n=6）和对照组（CN，n=5）。前大鼠被关在带有滚轮（SN-451）的笼子里40天，允许它们进行自愿运动，而CN大鼠被锁在带有滚轮的笼子里。在第40天，毛果芸香碱诱导的唾液测量如下。简单地说，将大鼠麻醉，将预先称重的棉花置于舌下，并腹腔注射匹罗卡品（0.5 mg/kg）以诱导唾液分泌。然后每10分钟更换一个棉球，持续1小时。再次称量收集的棉球，并通过从最终重量中减去初始重量来计算分泌的唾液质量。
• 参考文献:

  [1]. Matsuzaki K, et al. Daily voluntary exercise enhances pilocarpine-induced saliva secretion and aquaporin 1 expression in rat submandibular glands. FEBS Open Bio. 2017 Dec 7;8(1):85-93.

  [2]. Yuan XL, et al. Cytotoxicity of pilocarpine to human corneal stromal cells and its underlying cytotoxic mechanisms. Int J Ophthalmol. 2016 Apr 18;9(4):505-11.

  [3]. Tonta MA, et al. Pilocarpine-induced relaxation of rat tail artery by a non-cholinergic mechanism and in the absence of an intact endothelium. Br J Pharmacol. 1994 Jun;112(2):525-32.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : TK1400000 CHEMICAL NAME : Pilocarpine CAS REGISTRY NUMBER : 92-13-7 LAST UPDATED : 199701 DATA ITEMS CITED : 14 MOLECULAR FORMULA : C11-H16-N2-O2 MOLECULAR WEIGHT : 208.29 WISWESSER LINE NOTATION : T5OVTJ C2 D1- DT5N CNJ C1 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Human DOSE/DURATION : 143 ug/kg TOXIC EFFECTS : Behavioral - coma Lungs, Thorax, or Respiration - cyanosis Vascular - BP elevation not characterized in autonomic section REFERENCE : CONEAT Confinia Neurologica. (Basel, Switzerland) V.1-37, 1938-75. Volume(issue)/page/year: 10,8,1949 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Human - woman DOSE/DURATION : 1143 ug/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - dyspnea Gastrointestinal - changes in structure or function of salivary glands Skin and Appendages - sweating REFERENCE : AROPAW Archives of Ophthalmology (Chicago). (AMA, 535 N. Dearborn St., Chicago, IL 60610) New series: V.1-44(3), 1929-50; V.64- 1960- Volume(issue)/page/year: 105,25,1987 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Human - man DOSE/DURATION : 1912 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : 85DCAI "Poisoning; Toxicology, Symptoms, Treatments," 2nd ed., Arena, J.M., Springfield, IL, C.C. Thomas, 1970 Volume(issue)/page/year: 2,73,1970 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 402 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value 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: 12,1204,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 166 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,APP-16,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 366 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,APP-16,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 88500 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,APP-16,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 119 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,APP-16,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 220 mg/kg TOXIC EFFECTS : Nutritional and Gross Metabolic - body temperature decrease REFERENCE : AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 192,88,1971 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 90900 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,APP-16,1982 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 61900 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,APP-16,1982 TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 120 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : HBAMAK "Abdernalden's Handbuch der Biologischen Arbeitsmethoden." (Leipzig, Ger. Dem. Rep.) Volume(issue)/page/year: 4,1386,1935 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3227 No. of Facilities: 11 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 115 (estimated) No. of Female Employees: 47 (estimated)

安全

• 符号: GHS06
• 信号词: Danger
• 危害声明: H300 + H330
• 警示性声明: P260-P264-P284-P301 + P310-P310
• 危害码 (欧洲): T+: Very toxic;
• 风险声明 (欧洲): 26/28
• 安全声明 (欧洲): 25-45
• 危险品运输编码: UN 1544
• 包装等级: III
• 危险类别: 6.1(b)

合成路线

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