Isoptpo Hyoscine | 51-34-3

• 物质功能分类: 原料药 - 神经系统用药 - 拟胆碱药
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: Isoptpo Hyoscine
• 英文别名: [(1S,2S,4S,5S)-9-methyl-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-7-yl] (2S)-3-hydroxy-2-phenylpropanoate
• CAS: 51-34-3
• 化学式: C₁₇H₂₁NO₄
• 分子量: 303.35
• InChiKey: STECJAGHUSJQJN-YXMSTPNBSA-N

物化性质

• 熔点：
  59 ºC
• 比旋光度：
  D20 -28° (c = 2.7)
• 沸点：
  444.28°C (rough estimate)
• 密度：
  1.31
• 闪点：
  232.2℃
• 溶解度：
  易溶于水，易溶于乙醇（96%）。
• LogP：
  0.980
• 颜色/状态：
  Viscous liquid
• 蒸汽压力：
  7.18X10-9 mm Hg at 25 °C (est)
• 稳定性/保质期：
  The commercially available transdermal system of scopolamine should be stored at controlled room temperature between 20 and 25 °C. Scopolamine hydrobromide should be stored in tight, light-resistant containers. Scopolamine hydrobromide injections should be stored in light-resistant, single-dose or multiple-dose containers, preferably of USP Type I glass, at 15 to 30 °C; freezing of the injections should be avoided. Commercially available scopolamine hydrobromide soluble tablets should be stored at controlled room temperature (15 to 30 °C).
• 旋光度：
  Specific optical rotation: -28 deg at 20 °C/D ( c = 2.7)
• 解离常数：
  pKa = 7.75

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  62.3
• 氢给体数：
  1
• 氢受体数：
  5

ADMET

代谢

尽管尚未完全确定东莨菪碱的代谢和排泄命运，但认为该药物几乎完全在肝脏代谢（主要通过结合）并随尿液排出。

Although the metabolic and excretory fate of scopolamine has not been fully determined, the drug is thought to be almost completely metabolized (principally by conjugation) in the liver and excreted in urine.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用概述：目前没有关于在母乳喂养期间使用东莨菪碱的信息。在分娩期间使用似乎对新生儿哺乳行为有不利影响。长期使用东莨菪碱可能会减少乳汁产生或乳汁排放，但单次系统性或眼用剂量不太可能干扰母乳喂养。在长期使用期间，观察乳汁减少的迹象（例如，不饱，体重增长不良）。为了在使用眼药水后显著减少到达母乳中的药物量，在眼角处对泪点施加压力1分钟或更长时间，然后用吸收性纸巾去除多余的溶液。 ◉ 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：抗胆碱药可以在动物中抑制泌乳，这显然是通过抑制生长激素和催产素的分泌。[1][2][3][4][5] 抗胆碱药还可以减少非哺乳妇女的血清催乳素水平。[6] 在已经建立泌乳的母亲中，催乳素水平可能不会影响她的哺乳能力。 在伊朗中部两家医院进行的一项回顾性病例对照研究比较了4组经阴道分娩的单胎足月健康初产妇在分娩后前2小时内的哺乳行为。这些组别包括在分娩期间未接受任何药物、接受催产素加东莨菪碱、接受催产素加美沙酮以及接受催产素、东莨菪碱和美沙酮的产妇。未用药组婴儿的表现优于所有其他组，而催产素加东莨菪碱组的表现优于接受了美沙酮的组。[7]

◉ Summary of Use during Lactation:No information is available on the use of scopolamine during breastfeeding. Use during labor appears to have a detrimental effect on newborn infants' nursing behavior. Long-term use of scopolamine might reduce milk production or milk letdown, but a single systemic or ophthalmic dose is not likely to interfere with breastfeeding. During long-term use, observe for signs of decreased lactation (e.g., insatiety, poor weight gain). To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Anticholinergics can inhibit lactation in animals, apparently by inhibiting growth hormone and oxytocin secretion.[1][2][3][4][5] Anticholinergic drugs can also reduce serum prolactin in nonnursing women.[6] The prolactin level in a mother with established lactation may not affect her ability to breastfeed. A retrospective case-control study conducted in two hospitals in central Iran compared breastfeeding behaviors in the first 2 hours postdelivery by infants of 4 groups of primiparous women with healthy, full-term singleton births who had vaginal deliveries. The groups were those who received no medications during labor, those who received oxytocin plus scopolamine, those who received oxytocin plus meperidine, and those who received oxytocin, scopolamine and meperidine. The infants in the no medication group performed better than those in all other groups, and the oxytocin plus scopolamine group performed better than the groups that had received meperidine.[7]

来源:Drugs and Lactation Database (LactMed)

毒理性

• 相互作用

莨菪碱在与可能引起中枢神经系统（CNS）作用的药物联合使用时应谨慎，如镇静剂、安眠药或酒精。特别注意与其他具有抗胆碱性质的药物可能发生的相互作用，例如其他颠茄生物碱、抗组胺药（包括美克洛嗪）、三环类抗抑郁药和肌肉松弛剂。

Scopolamine should be used with care in patients taking other drugs that are capable of causing CNS effects such as sedatives, tranquilizers, or alcohol. Special attention should be paid to potential interactions with drugs having anticholinergic properties; e.g., other belladonna alkaloids, antihistamines (including meclizine), tricyclic antidepressants, and muscle relaxants.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在同时使用阿托品的情况下，由于胃动力下降和胃排空延迟，口服药物的吸收可能会减少。

The absorption of oral medications may be decreased during the concurrent use of scopolamine because of decreased gastric motility and delayed gastric emptying.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

抗胆碱药和皮质类固醇的联合使用可能会导致眼内压升高。/抗胆碱药/解痉药/

Concomitant administration of antimuscarinics and corticosteroids may result in increased intraocular pressure. /Antimuscarinics/Antispasmodics/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

Antacids may decrease the extent of absorption of some oral antimuscarinics when these drugs are administered simultaneously. Therefore, oral antimuscarinics should be administered at least 1 hour before antacids. Antimuscarinics may be administered before meals to prolong the effects of postprandial antacid therapy. However, controlled studies have failed to demonstrate a substantial difference in gastric pH when combined antimuscarinic and antacid therapy was compared with antacid therapy alone. /Antimuscarinics/Antispasmodics/ 碳酸氢钠可能会减少某些口服抗胆碱能药物的吸收量，当这些药物同时给药时。因此，口服抗胆碱能药物应在碳酸氢钠之前至少1小时给药。抗胆碱能药物可以在餐前给药，以延长餐后碳酸氢钠疗法的效果。然而，对照研究未能显示出当联合抗胆碱能和碳酸氢钠疗法与单独碳酸氢钠疗法相比，在胃pH方面有显著差异。/抗胆碱能药物/解痉药/

Antacids may decrease the extent of absorption of some oral antimuscarinics when these drugs are administered simultaneously. Therefore, oral antimuscarinics should be administered at least 1 hour before antacids. Antimuscarinics may be administered before meals to prolong the effects of postprandial antacid therapy. However, controlled studies have failed to demonstrate a substantial difference in gastric pH when combined antimuscarinic and antacid therapy was compared with antacid therapy alone. /Antimuscarinics/Antispasmodics/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

氢溴酸东莨菪碱通过肌肉注射或皮下注射后能够迅速吸收。该药物从胃肠道吸收良好，主要从上部小肠吸收。氢溴酸东莨菪碱也能通过皮肤很好地吸收。在使用透皮贴剂后，氢溴酸东莨菪碱在4小时内可以在血浆中检测到，平均在24小时内达到峰值浓度。在一项针对健康个体的研究中，报告了在单次使用透皮贴剂后24小时内的平均游离和总（游离加结合）血浆氢溴酸东莨菪碱浓度分别为87和354皮克/毫升，该透皮贴剂大约每72小时提供1毫克氢溴酸东莨菪碱。/氢溴酸东莨菪碱/

Scopolamine hydrobromide is rapidly absorbed following IM or subcutaneous injection. The drug is well absorbed from the GI tract, principally from the upper small intestine. Scopolamine also is well absorbed percutaneously. Following topical application behind the ear of a transdermal system, scopolamine is detected in plasma within 4 hours, with peak concentrations occurring within an average of 24 hours. In one study in healthy individuals, mean free and total (free plus conjugated) plasma scopolamine concentrations of 87 and 354 pg/mL, respectively, have been reported within 24 hours following topical application of a single transdermal scopolamine system that delivered approximately 1 mg/72 hours. /Scopolamine hydrobromide/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在一名个体口服0.906毫克东莨菪碱后，大约在1小时内达到约2纳克/毫升的峰值浓度。尽管商业上可用的透皮系统含有1.5毫克的东莨菪碱，但膜控制扩散系统旨在以大约恒定的速率在72小时内向系统循环释放大约1毫克的药物。系统粘合层最初在6小时内以受控的、渐近下降的速率释放0.14毫克的东莨菪碱作为初始引导剂量；然后，剩余的剂量以大约5微克/小时的速率在系统剩余的66小时有效寿命内释放。制造商表示，初始引导剂量饱和皮肤上的结合位点，并迅速使血浆浓度达到稳态。在一项交叉研究中，比较了健康个体在多个12小时收集间隔期间东莨菪碱的尿排泄率，稳态（24-72小时）期间药物排泄率在恒速静脉输注（3.7-6微克/小时）和透皮给药之间没有差异。透皮系统似乎以与恒速静脉输注相同的速率将药物输送到系统循环；然而，相对较长的收集间隔（12小时）使得精确解释数据变得困难。在12至24小时的给药期间和72小时后，东莨菪碱的排泄率透皮系统高于恒速静脉输注。

Following oral administration of a 0.906-mg dose of scopolamine in one individual, a peak concentration of about 2 ng/mL was reached within 1 hour. Although the commercially available transdermal system contains 1.5 mg of scopolamine, the membrane-controlled diffusion system is designed to deliver approximately 1 mg of the drug to systemic circulation at an approximately constant rate over a 72-hour period. An initial priming dose of 0.14 mg of scopolamine is released from the adhesive layer of the system at a controlled, asymptotically declining rate over 6 hours; then, the remainder of the dose is released at an approximate rate of 5 ug/hour for the remaining 66-hour functional lifetime of the system. The manufacturer states that the initial priming dose saturates binding sites on the skin and rapidly brings the plasma concentration to steady-state. In a crossover study comparing urinary excretion rates of scopolamine during multiple 12-hour collection intervals in healthy individuals, there was no difference between the rates of excretion of drug during steady-state (24-72 hours) for constant-rate IV infusion (3.7-6 mcg/hour) and transdermal administration. The transdermal system appeared to deliver the drug to systemic circulation at the same rate as the constant-rate IV infusion; however, relatively long collection intervals (12 hours) make it difficult to interpret the data precisely. During the 12- to 24-hour period of administration and after 72 hours, the rate of excretion of scopolamine was higher with the transdermal system than with the constant-rate IV infusion.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

药物在体内的分布尚未得到充分研究。药物似乎可以可逆地与血浆蛋白结合。由于药物可以引起中枢神经系统的作用，它显然能够穿过血脑屏障。据报道，该药物也能穿过胎盘，并分布到乳汁中。

The distribution of scopolamine has not been fully characterized. The drug appears to be reversibly bound to plasma proteins. Scopolamine apparently crosses the blood-brain barrier since the drug causes CNS effects. The drug also reportedly crosses the placenta and is distributed into milk..

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

尽管尚未完全确定东莨菪碱的代谢和排泄命运，但认为该药物几乎完全在肝脏代谢（主要通过结合反应）并由尿液排出。在一项研究中，单次口服给药后，仅有小部分剂量（大约4-5%）在50小时内以原形从尿液中排出；未改变药物的尿清除率约为120 mL/分钟。在另一项研究中，在皮下注射或口服给药后72小时内，未改变的剂量有3.4%或不到1%从尿液中排出。在健康个体应用单次透皮东莨菪碱系统，该系统大约每72小时提供1 mg，自由和总（自由加结合）东莨菪碱的尿排泄率分别为约0.7和3.8微克/小时。移除透皮东莨菪碱系统后，透皮系统应用部位皮肤受体的结合东莨菪碱耗尽导致血浆东莨菪碱浓度呈对数线性下降。在108小时内，少于10%的总剂量以未改变药物及其代谢物的形式从尿液中排出。

Although the metabolic and excretory fate of scopolamine has not been fully determined, the drug is thought to be almost completely metabolized (principally by conjugation) in the liver and excreted in urine. Following oral administration of a single dose of scopolamine in one study, only small amounts of the dose (about 4-5%) were excreted unchanged in urine within 50 hours; urinary clearance of unchanged drug was about 120 mL/minute. In another study, 3.4% or less than 1% of a single dose was excreted unchanged in urine within 72 hours following subcutaneous injection or oral administration of the drug, respectively. Following application of a single transdermal scopolamine system that delivered approximately 1 mg/72 hours in healthy individuals, the urinary excretion rate of free and total (free plus conjugated) scopolamine was about 0.7 and 3.8 ug/hour, respectively. Following removal of the transdermal system of scopolamine, depletion of scopolamine bound to skin receptors at the site of the application of the transdermal system results in a log-linear decrease in plasma scopolamine concentrations. Less than 10% of the total dose is excreted in urine as unchanged drug and its metabolites over 108 hours.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  T+
• 安全说明：
  S25,S45
• 危险类别码：
  R26/27/28
• 海关编码：
  29399990
• 危险品运输编号：
  UN 1544PSN2 6.1 / PGII

制备方法与用途

药理作用

东莨菪碱是一种叔胺类抗毒蕈碱药，其作用一般类似于阿托品。它不仅对中枢神经系统和周围组织均有影响，而且在抑制唾液分泌方面比阿托品更显著。通常，小剂量的东莨菪碱会减缓心率而非加速心率。与阿托品相比，东莨菪碱对大脑皮质具有更强的抑制作用，产生嗜睡和健忘的症状。其对眼平滑肌及腺体分泌的抑制效果也比阿托品更显著。

除了对外周平滑肌有解痉作用外，东莨菪碱还能阻断神经节和神经-肌肉接头的作用，并且其在中枢神经系统中的影响相对较弱。相较于阿托品，它的散瞳、调节麻痹及抑制分泌的效果更为强烈，但持续时间较短。与阿托品兴奋大脑相反，东莨菪碱展现出显著的镇静作用。

东莨菪碱在外周作用上与阿托品相似，能够更有效地抑制涎腺、支气管和汗腺的分泌，并迅速产生散瞳及调节麻痹的效果，但这些效果消失得也更快。它对心脏、肠管和支气管平滑肌的作用较弱。此外，东莨菪碱还具有解除血管痉挛和改善微循环的作用。

在一般治疗剂量下，它对外周神经有明显的抑制作用；较大剂量时会产生催眠作用。大剂量使用可能会导致激动、不安、幻觉或谵妄等中枢兴奋症状，但很快会进入睡眠状态。如果剂量进一步增大（如0.08mg/kg静脉注射），则对皮质的抑制作用更为显著。当与氯丙嗪联合使用时，可能迅速产生麻痹现象。

在呼吸兴奋、抗晕动和抗震颤麻痹方面，东莨菪碱的效果通常低于阿托品。

研发背景

东莨菪碱的研发历史可以追溯到1892年，当时E.施密特首次从东莨菪中分离出该成分。后来的研究表明，它与阿托品具有相似的作用机制，但在眼部、心率减缓以及对大脑皮质的抑制作用方面存在差异。

近年来，关于东莨菪碱的研发取得了新的进展。西南大学和中科院昆明植物所合作解析了其生物合成步骤及莨菪碱脱氢酶催化机制，并在《自然》杂志上发表了相关论文。此外，斯坦福大学通过使用合成生物学技术，在酵母中从头合成了东莨菪碱及其衍生物，并利用这些化合物开发出新型药物和生物传感器。

药物不良反应与禁忌症

东莨菪碱的常见不良反应包括恶心、呕吐、瞳孔缩小、流涎、癫痫发作、尿失禁、呼吸困难、心动过缓及腹泻等。局部用于眼部时，患者难以耐受，可能导致结膜产生结膜滤泡。注射剂中的亚硫酸钠常会引起过敏反应，甚至导致全身性过敏。

使用东莨菪碱的禁忌症包括对东莨菪碱过敏者、哺乳期妇女、胃肠道梗阻、尿路梗阻、哮喘、糖尿病患者以及正在使用胆碱酯酶或除极神经肌肉阻断剂的人群。

化学性质

东莨菪碱是一种白色结晶性粉末，主要存在于茄科植物东莨菪、洋金花和曼陀罗中。它微溶于水，易溶于乙醇，并极易溶于氯仿和二氯甲烷。同时也能溶解在不挥发性油和苯中。

该化合物含有吲哚环和吡咯环结构特点，具有手型碳，左旋体活性更强，属于莨菪烷类生物碱。

用途

东莨菪碱是颠茄植物中最有效的生物碱之一，用于阻断副交感神经系统。它也可用作中枢神经系统的抑制剂，作用类似于颠茄碱但更为强烈且持续时间较短。临床上通常使用其氢溴酸盐形式，可用于麻醉镇痛、止咳、平喘，并对动晕症有效。

此外，东莨菪碱还可用于控制帕金森病的僵硬和震颤症状。

类别与毒性

东莨菪碱被归类为有毒物质。它具有中毒性质，急性口服毒性实验显示，在大鼠中的半数致死量（LD50）约为2650毫克/公斤；在小鼠中则为4小时吸入4毫升/立方米的空气。

该物质可燃，并且在火场会分解产生有毒氮氧化物烟雾。因此，储存和运输时应保持低温、通风和干燥环境以确保安全。

灭火剂推荐使用水、二氧化碳、干粉或砂土等方法进行扑灭火灾。