Guanadrel Sulfate | 22195-34-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Guanadrel Sulfate
• 英文别名: 2-(1,4-dioxaspiro[4.5]decan-3-ylmethyl)guanidine;sulfuric acid
• CAS: 22195-34-2
• 化学式: C20H40N6O8S
• 分子量: 524.6
• InChiKey: RTEVGQJRTFFMLL-UHFFFAOYSA-N

物化性质

• 熔点：
  213.5-215°
• 颜色/状态：
  White to off-white crystalline powder
• 溶解度：
  In water, 76 mg/ml @ 25 °C
• 稳定性/保质期：
  Guanadrel sulfate tablets should be stored in well-closed containers at a temperature less than 40 °C, preferably between 15-30 °C.

计算性质

• 辛醇/水分配系数(LogP)：
  0.02
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  249
• 氢给体数：
  6
• 氢受体数：
  10

ADMET

代谢

大约40-50%的药物在肝脏中代谢为2,3-二羟基丙基胍和几种未识别的代谢物。这些代谢物的降压活性尚不清楚。

Approximately 40-50% of the drug is metabolized in the liver to 2,3-dihydroxypropylguanidine and several unidentified metabolites. The hypotensive activity of the metabolites is not known.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

三环类抗抑郁药、吩噻嗪类药物以及间接作用的拟交感神经药（例如，麻黄碱、苯丙醇胺）可能会阻止胍那苄进入肾上腺素能神经元或逆转胍那苄的降压效果。麻黄碱已被证明能迅速逆转胍那苄的药理作用。胍那苄可能会增强直接作用的拟交感神经药物（如去甲肾上腺素或苯肾上腺素）的药理活性。

Tricyclic antidepressants, phenothiazines, and indirect-acting sympathomimetics (eg, ephedrine, phenylpropanolamine) may block the uptake of guanadrel into adrenergic neurons or reverse the hypotensive effect of guanadrel. Ephedrine has been shown to rapidly reverse the pharmacologic effects of guanadrel. Guanadrel may potentiate the pharmacologic activity of direct-acting sympathomimetic agents such as norepinephrine or phenylephrine.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

单胺氧化酶抑制剂据报道会对抗胍乙定的降压效果；胍乙定在正在接受MAO抑制剂的患者中是禁忌的，并且这些药物在给予胍乙定之前应至少停用1周。

Monoamine oxidase inhibitors reportedly antagonize the hypotensive effect of guanadrel; ... guanadrel is contraindicated in patients receiving MAO inhibitors and that these drugs should be discontinued for at least 1 week prior to administration of guanadrel.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

去甲肾上腺素类药物应谨慎使用，因为甘氨瑞林可能会增强这些药物的升压作用和致心律失常反应。

Vasopressors should be administered with caution since guanadrel may enhance the pressor and arrhythmogenic responses to these drugs.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在停用三环类抗抑郁药治疗时，接受胍那苄的患者应特别小心，尤其是如果突然停用抗抑郁药，因为胍那苄的增强临床效果（例如，低血压）可能会发生。由于许多非处方感冒、过敏和哮喘制剂含有拟交感神经药，接受胍那苄治疗的患者应被告知，除非先咨询他们的医生或药剂师，否则不要使用这些制剂进行自我药疗。

Caution should be exercised when tricyclic antidepressant therapy is discontinued in patients receiving guanadrel, particularly if discontinuance of the antidepressant is abrupt, since enhanced clinical effects (e.g., hypotension) of guanadrel may occur. Because many nonprescription cold, allergy, and asthma preparations contain sympathomimetic agents, patients receiving guanadrel should be warned not to use these preparations for self-medication unless first consulting with their physician or pharmacist.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

过量服用最重要的并发症是严重的低血压（通常是体位性）。低血压应通过使用特伦德伦堡体位来治疗，必要时应给予静脉输液。

The most important complication of overdose being profound hypotension (usually orthostatic). ...Hypotension should be treated by the use of Trendelenburg position, and iv fluids should be administered when necessary.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

硫酸胍那苄迅速且几乎完全通过口服给药被吸收。通常在口服给药后1.5-2小时达到血浆峰浓度。硫酸胍那苄的降压效果通常在0.5-2小时内开始，4-6小时达到峰值，并持续4-14小时。

Guanadrel sulfate is rapidly and almost completely absorbed following oral administration. Peak plasma concentrations usually are achieved 1.5-2 hr after oral administration. The hypotensive effect of guanadrel sulfate usually has an onset of 0.5-2 hrs, peaks at 4-6 hr, and persists for 4-14 hr.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

大约20%的冠脉素与血浆蛋白结合，浓度范围广泛。该药物广泛分布到大多数身体组织和液体中。药物很少，如果有的话，穿过血脑屏障或分布到眼睛中。目前尚不清楚冠脉素是否分布到乳汁中或穿过人类胎盘。在小鼠中，该药物已显示以小浓度穿过胎盘。

Approximately 20% of guanadrel is bound to plasma proteins over a wide concentration range. The drug is widely distributed into most body tissues and fluids. Little, if any, of the drug crosses the blood-brain barrier or distributes into the eye. It is not known whether guanadrel is distributed into milk or crosses the placenta in humans. The drug has been shown to cross the placenta in small concentrations in mice

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

冠纳德雷尔通过肾脏和非肾脏途径从体内清除。在肾功能不全的患者中，其消除功能受损；在一组平均肌酐清除率为每分钟13毫升的患者中，总体清除率降低了4到5倍。

Guanadrel is cleared from the body by both renal and nonrenal disposition. Its elimination is impaired in patients with renal insufficiency; total-body clearance was reduced by 4- to 5-fold in a group of patients with a clearance of creatinine averaging 13 ml per minute.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

大约40-50%的药物在肝脏中代谢……。关阿德拉及其代谢物主要通过尿液排出。大约85%的口服剂量在24小时内通过尿液排出；40-50%的剂量以原形通过尿液排出。

Approximately 40-50% of the drug is metabolized in the liver ... . Guanadrel and its metabolites are excreted principally in urine. Approximately 85% of an oral dose of the drug is excreted in urine within 24 hrs; 40-50% of the dose is excreted in urine unchanged.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为产物：
  描述：

  1,4-Dioxa-spiro[4.5]dec-2-ylmethyl-cyanamide 生成 Guanadrel Sulfate
  参考文献：
  名称：

  Bioorg. Med. Chem. Lett. 2001, 11, 2377-2380

  摘要：

  DOI：

文献信息

• GB1197313A
  申请人：——

  公开号：——

  公开（公告）日：——
• NOVEL GENES AND MARKERS IN TYPE 2 DIABETES AND OBESITY
  申请人：Oy Jurilab Ltd

  公开号：EP2021502A1

  公开（公告）日：2009-02-11
• US7790905B2
  申请人：——

  公开号：US7790905B2

  公开（公告）日：2010-09-07
• US7927613B2
  申请人：——

  公开号：US7927613B2

  公开（公告）日：2011-04-19
• [EN] NOVEL GENES AND MARKERS IN TYPE 2 DIABETES AND OBESITY<br/>[FR] GÈNES ET MARQUEURS ATYPIQUES DANS LE DIABÈTE DE TYPE 2 ET L'OBÉSITÉ
  申请人：JURILAB LTD OY

  公开号：WO2007128884A1

  公开（公告）日：2007-11-15

  [EN] Genes, SNP markers and haplotypes of susceptibility or predisposition to T2D and subdiagnosis of T2D and related medical conditions are disclosed. Methods for diagnosis, 5 prediction of clinical course and efficacy of treatments for T2D, obesity and related phenotypes using polymorphisms in the risk genes are also disclosed. The genes, gene products and agents of the invention are also useful for monitoring the effectiveness of prevention and treatment of T2D and related traits. Kits are also provided for the diagnosis, selecting treatment and assessing prognosis of T2D. Novel methods for prevention and 10 treatment of metabolic diseases such as T2D based on the disclosed T2D genes, polypeptides and related pathways are also disclosed.
  [FR] La présente invention concerne des gènes, des marqueurs SNP et des haplotypes de susceptibilité ou de prédisposition au DT2 et le sous-diagnostic du DT2 et de conditions médicales associées. Des procédés de diagnostic, (5) de prédiction d'évolution clinique et d'efficacité des traitements du DT2, de l'obésité et de phénotypes associés utilisant des polymorphismes dans les gènes à risque sont également présentés. Les gènes, produits et agents génétiques de l'invention sont aussi utiles pour contrôler l'efficacité de la prévention et du traitement du DT2 et des traits qui lui sont associés. Des kits sont également fournis pour le diagnostic, la sélection de traitement et l'évaluation d'un pronostic de DT2. Des procédés atypiques pour la prévention et (10) le traitement de maladies métaboliques telles que le DT2 basés sur les gènes DT2 révélés, les polypeptides et voies associées sont également présentés.