Nicotine hydrogen tartrate | 65-31-6

• 物质功能分类: 天然产物 - 生物碱
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: Nicotine hydrogen tartrate
• 英文别名: (2R,3R)-2,3-dihydroxybutanedioic acid;3-[(2S)-1-methylpyrrolidin-2-yl]pyridine
• CAS: 65-31-6；6550-19-2；3275-73-8；2624-48-8
• 化学式: C10H16N2(C4H5O6)2
• 分子量: 462.4
• InChiKey: RFEJUZJILGIRHQ-OMDKHLBYSA-N

物化性质

• 熔点：
  90°
• 比旋光度：
  D20 +26° (c = 10)
• 溶解度：
  H2O:50 mg/mL
• 物理描述：
  WHITE FLAKES.
• 颜色/状态：
  White plates
• 自燃温度：
  244 °C
• 分解：
  When heated to decomposition it emits toxic fumes of /nitrogen oxides and carbon monoxide/.

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  246
• 氢给体数：
  8
• 氢受体数：
  14

ADMET

代谢

在人体内，尼古丁会代谢成可替宁、羟基可替宁、去甲基可替宁以及其他未识别的化合物... 在其他使用放射性碳(14)标记的尼古丁的研究中，静脉注射后从尿液中分离出了尼古丁异甲基铵离子。

In man, nicotine is metabolized to cotinine, hydroxycotinine, desmethylcotinine, and other unidentified compounds ... In other studies with (14)C-labeled nicotine, nicotine isomethonium ion was isolated from urine after iv administration.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 暴露途径

该物质可以通过吸入其气溶胶、通过皮肤接触以及摄入进入人体。

The substance can be absorbed into the body by inhalation of its aerosol, through the skin and by ingestion.

来源:ILO-WHO International Chemical Safety Cards (ICSCs)

毒理性

• 吸入症状

恶心。呕吐。腹痛。头痛。抽搐。

Nausea. Vomiting. Abdominal pain. Headache. Convulsions.

来源:ILO-WHO International Chemical Safety Cards (ICSCs)

毒理性

• 皮肤症状

可能会被吸收！红色。疼痛。见吸入。

MAY BE ABSORBED! Redness. Pain. See Inhalation.

来源:ILO-WHO International Chemical Safety Cards (ICSCs)

毒理性

• 眼睛症状

疼痛。红肿。

Pain. Redness.

来源:ILO-WHO International Chemical Safety Cards (ICSCs)

毒理性

• 摄入症状

见吸入。

See Inhalation.

来源:ILO-WHO International Chemical Safety Cards (ICSCs)

吸收、分配和排泄

对尼古丁酒石酸盐的抗痛作用进行了研究，以确定其在中枢神经系统中的定位。在向颈总动脉、脊椎动脉和蛛网膜下腔注射(3)H-尼古丁后，进行了抗痛作用和生物分布研究。当(3)H-尼古丁注射到蛛网膜下腔时，其效果比通过任何其他给药途径更为显著。此外，分布研究显示(3)H-尼古丁几乎完全包含在胸椎和腰椎区域。显然，脊髓是尼古丁引起抗痛作用的重要部位。

Studies were conducted to localize the antinociceptive action of nicotine ditartrate within the central nervous system. Antinociceptive and biodispositional studies were carried out after the injection of (3)H-nicotine sc and intracerebroventricularly into the common carotid and vertebral arteries and into the subarachnoid space. (3)H-nicotine was more potent when given into the subarachnoid space than by any other route of administration. Further, disposition studies showed that (3)H-nicotine was almost entirely contained in the thoracic and lumbar areas. Apparently, the spinal cord is an important site for antinociception induced by nicotine.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

当前研究的目的是确定尼古丁通过亲水性液体灌肠（酸性和碱性）、疏水性液体灌肠（酸性和碱性）以及口服和静脉给药途径的生物利用度和药代动力学参数。三十名健康志愿者接受了一种五种配方中的一种（每种 n = 6）：亲水性酸性液体灌肠、亲水性碱性液体灌肠、疏水性酸性液体灌肠、疏水性碱性液体灌肠和口服溶液，剂量为45微克尼古丁碱/千克（作为尼古丁酒石酸盐）。在另一独立的研究期间，所有参与者还接受了15微克尼古丁碱/千克（作为尼古丁酒石酸盐）的静脉注射。通过气相色谱-质谱法测定血清中尼古丁的浓度。液体灌肠配方给药后尼古丁的平均（+/-SD）生物利用度（亲水性酸性17 +/- 18%，亲水性碱性16 +/- 16%，疏水性酸性25 +/- 17%，疏水性碱性15 +/- 12%）与口服溶液给药后尼古丁的生物利用度相似（20 +/- 25%）。所有五种非静脉给药途径的尼古丁生物利用度显著低于静脉给药的尼古丁（100%）。血清中尼古丁的浓度并不能预测不良反应。无论是作为液体灌肠还是口服溶液给药，尼古丁酒石酸盐的生物利用度都较低，并且耐受性良好。

...The purpose of the current study was to determine the bioavailability and pharmacokinetic parameters of nicotine after administration by hydrophilic liquid enema (acidic and basic), hydrophobic liquid enema (acidic and basic), and by oral and intravenous routes. Thirty healthy volunteers received 45 ug nicotine base/kg (as nicotine tartrate) in one of five formulations (each n = 6): hydrophilic acidic liquid enema, hydrophilic basic liquid enema, hydrophobic acidic liquid enema, hydrophobic basic liquid enema, and oral solution. All participants also received 15 ug nicotine base/kg (as nicotine tartrate) intravenously during a separate study period. Serum concentrations of nicotine were determined by gas chromatography with mass spectrometry. The mean (+/-SD) bioavailabilities of nicotine after administration in the liquid enema formulations (hydrophilic acidic 17 +/- 18%, hydrophilic basic 16 +/- 16%, hydrophobic acidic 25 +/- 17%, hydrophobic basic 15 +/- 12%) were similar to the bioavailability of nicotine after administration by oral solution (20 +/- 25%). The bioavailabilities of nicotine for all five nonintravenous formulations were significantly less than for intravenous nicotine (100%). Serum concentrations of nicotine did not predict adverse reactions. Nicotine tartrate administered as either a liquid enema or as an oral solution had low bioavailability and was well tolerated. ...

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

实验比较了小剂量和大剂量放射性尼古丁酒石酸盐给药后，幼年和成年小鼠血液、心脏和大脑中尼古丁浓度随时间的变化。在一些实验中，使用美卡拉明或六甲铵阻断尼古丁受体，并测量它们对尼古丁水平的影响。尼古丁引起的震颤通过视觉观察，并通过心电图测量其对心率的影响。在成年小鼠中，大脑尼古丁的峰值出现在10分钟，而在幼年小鼠中，大脑尼古丁水平在20分钟时仍在上升。在后一种情况下，血液和心脏的尼古丁水平高于相应的大脑水平，脑干中的尼古丁水平超过了大脑半球的水平。成年小鼠的结果则相反。在幼年小鼠心脏中测量到了显著的尼古丁积累。美卡拉明预处理降低了成年小鼠大脑中的尼古丁水平，而在幼年小鼠中，血液和心脏中的尼古丁水平也有所降低。这种预处理同样在两个年龄组中消除了尼古丁震颤及其对心率的影响。这表明，美卡拉明处理后幼年和成年小鼠尼古丁水平的差异可能不仅取决于可能的循环变化差异，还可能代表“受体群体”的差异。六甲铵没有消除尼古丁对心率的中枢抑制效应，也没有降低大脑中的尼古丁水平。

Experiments were done to compare the time-courses of the nicotine concentration in the blood, heart, and brain of infant and adult mice after small and large single doses of radioactive nicotine tartrate. In some experiments the nicotine receptors were blocked with mecamylamine or hexamethonium, and their effects on nicotine levels were measured. The nicotine-induced tremor was allowed visually, and its effects on the heart rate were measured by ECG. In adult mice the peak levels of brain nicotine occurred at 10 min, whereas in infant mice the brain nicotine levels were still rising at 20 min. In the latter the blood and heart nicotine levels were higher than the respective brain levels, and the nicotine level in the brain stem exceeded the hemisphere level. The results were reversed in adult mice. A remarkable accumulation of nicotine in the infant heart was measured. Pretreatment with mecamylamine lowered brain nicotine levels in adult mice, and in infant mice the nicotine levels in blood and heart were lowered as well. This pretreatment abolished the nicotine tremor and its effects on the heart rate similarly in both age groups. This suggests that the difference in nicotine levels after mecamylamine in infant and adult mice may not depend solely on possible differences in circulatory changes but can represent differences in "receptor population" as well. Hexamethonium did not abolish the central depressant effect of nicotine on the heart rate nor did it lower the brain nicotine levels. ...

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(a)
• 危险品标志：
  T+,N
• 安全说明：
  S13,S28,S45,S61
• 危险类别码：
  R26/27/28,R51/53
• WGK Germany：
  2
• RTECS号：
  QT0350000
• 包装等级：
  II
• 危险类别：
  6.1(a)
• 危险品运输编号：
  UN 1659 6.1/PG 2

制备方法与用途

概述

尼古丁俗名烟碱，属于吡啶衍生物类的生物碱，具有一定的碱性，能与酸反应生成胺盐。因此，烟碱盐（尼古丁盐）本质上是一种胺盐，相对于尼古丁本身而言，烟碱盐（尼古丁盐）对口腔或喉咙黏膜的刺激要小很多。

人体代谢

烟碱盐（尼古丁盐）进入人体后会分解成尼古丁和对应的酸。同等质量下，相比纯尼古丁，烟碱盐（尼古丁盐）进入体内的尼古丁量实际上较少，因为其中还包含酸的重量。因此，烟碱盐（尼古丁盐）通常可以加到50mg甚至接近100mg，但实际上真正含有的尼古丁量可能远低于此。在电子烟油中，烟碱盐（尼古丁盐）往往使用柠檬酸和酒石酸制成。

类别 有毒物品 毒性分级

高毒

急性毒性

• 口服-大鼠 LD50: 65毫克/公斤
• 口服-小鼠 LD50: 65毫克/公斤

储运特性

库房应通风、低温干燥；需与食品原料分开储运

灭火剂

砂土、水、泡沫、二氧化碳、干粉