Ouabain appears as odorless, white crystals or crystalline powder as an octahydrate. Used to produce rapid digitalization in acute congestive heart failure. Also recommended in treatment of atrial or nodal paroxysmal tachycardia and atrial flutter. (EPA, 1998)
颜色/状态：
Crystals from water
分解：
Melts with decomposition at 190 °C.
稳定性/保质期：
远离氧化物。
计算性质
辛醇/水分配系数(LogP)：
-1.7
重原子数：
41
可旋转键数：
4
环数：
6.0
sp3杂化的碳原子比例：
0.9
拓扑面积：
207
氢给体数：
8
氢受体数：
12
ADMET
代谢
乌巴因...并不广泛地与血浆白蛋白结合，并且...大部分以原形被排出。
Ouabain ... is not bound extensively to plasma albumin and ... /is/ excreted largely unchanged.
IDENTIFICATION AND USE: Ouabain, a solid, is a cardiac glycoside commonly used in the laboratory for electrophysiological experiments in cardiac myocytes. It has been used as medication and as a veterinary drug. HUMAN EXPOSURE AND TOXICITY: Ouabain-induced reactive oxygen species generation and cell apoptosis on human glioma cells has been described. The number of ouabain binding sites, detected using (3)H ouabain, were significantly increased in the borderline hypertensive subjects irrespective of heredity. Endogenous ouabain levels increase in human essential hypertension. ANIMAL STUDIES: Retinal activity measured by electroretinography in animals and in isolated retinas has been shown to be rapidly reduced by exposure to ouabain. Intravitreal injection in rabbits has caused rapid loss of vision. In cats circumferential artery of iris is reported to be constricted by ouabain. Ouabain is an endogenous Na(+)/K(+)-ATPase inhibitor whose chronic administration induces hypertension. Ouabain treatment in rats produced cognitive deficits independent of locomotor effects associated with bipolar disorder. ECOTOXICITY STUDIES: Ouabain inhibited the efflux of ammonia (from the basolateral to the apical side) in preparation of isolated Carcinus gills.
Intracerebroventricular (ICV) administration of ouabain, a specific Na-K-ATPase inhibitor, in rats mimics the manic phenotypes of bipolar disorder and thus has been proposed as one of the best animal models of mania. Bipolar mania has been known to be associated with dysfunctions of medial prefrontal cortex (mPFC), a brain area critically involved in mental functions; however, the exact mechanism underlying these dysfunctions is not yet clear. The present study investigated synaptic transmission, synaptic plasticity, and dopamine release in Sprague-Dawley rat mPFC following ICV administration of ouabain (5 uL of 1 mM ouabain). The electrophysiological results demonstrated that ouabain depressed the short- and the long-term synaptic plasticity, represented by paired-pulse facilitation and long-term potentiation, respectively, in the mPFC. These ouabain-induced alterations in synaptic plasticity can be prevented by pre-treatment with lithium (intraperitoneal injection of 47.5 mg/kg lithium, twice a day, 7 days), which acts as an effective mood stabilizer in preventing mania. The electrochemical results demonstrated that ICV administration of ouabain enhanced dopamine release in the mPFC, which was not affected by pre-treatment with lithium. These findings suggested that alterations in synaptic plasticity and dopamine release in the mPFC might underlie the dysfunctions of mPFC accompanied with ouabain administration-induced bipolar mania.
Brain-derived neurotrophic factor (BDNF) is a well-known and well-studied neurotrophin. Most biological effects of BDNF are mediated by the activation of TrkB receptors. This neurotrophin regulates several neuronal functions as cell proliferation, viability, and differentiation. Ouabain is a steroid that binds to the Na(+)/K(+) ATPase, inducing the activation of several intracellular signaling pathways. Previous data from our group described that ouabain treatment increases retinal ganglion cells survival (RGC). The aim of the present study was to evaluate, if this cardiac glycoside can have a synergistic effect with BDNF, the classical trophic factor for retinal ganglion cells, as well as investigate the intracellular signaling pathways involved. Our work demonstrated that the activation of Src, PLC, and PKCdelta participates in the signaling cascade mediated by 50 ng/mL BDNF, since their selective inhibitors completely blocked the trophic effect of BDNF. We also demonstrated a synergistic effect on RGC survival when we concomitantly used ouabain (0.75 nM) and BDNF (10 ng/mL). Moreover, the signaling pathways involved in this synergistic effect include Src, PLC, PKCdelta, and JNK. Our results suggest that the synergism between ouabain and BDNF occurs through the activation of the Src pathway, JNK, PLC, and PKCdelta.
The present study aimed to investigate the effects of mood stabilizers, specifically lithium (Li) and valproate (VPA), on mitochondrial superoxide, lipid peroxidation, and proteins involved in cell death signaling pathways in the brains of rats subjected to the ouabain-induced animal model of mania. Wistar rats received Li, VPA, or saline twice a day for 13 days. On the 7th day of treatment, the animals received a single intracerebroventricular injection of ouabain or aCSF. After the ICV injection, the treatment with mood stabilizers continued for 6 additional days. The locomotor activity of rats was measured using the open-field test. In addition, we analyzed oxidative stress parameters, specifically levels of phosphorylated p53 (pp53), BAX and Bcl-2 in the brain of rats by immunoblot. Li and VPA reversed ouabain-related hyperactivity. Ouabain decreased Bcl-2 levels and increased the oxidative stress parameters BAX and pp53 in the brains of rats. Li and VPA improved these ouabain-induced cellular dysfunctions; however, the effects of the mood stabilizers were dependent on the protein and brain region analyzed. These findings suggest that the Na(+)/K(+)-ATPase can be an important link between oxidative damage and the consequent reduction of neuronal and glial density, which are both observed in BD, and that Li and VPA exert protective effects against ouabain-induced activation of the apoptosis pathway.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
相互作用
Docosahexaenoic acid (DHA) may prevent heart failure or optimize drug treatments by improving cardiac contraction. We studied whether DHA-enriched avian glycerophospholipids (GPL-DHA) have cardioprotective effects in rats treated with ouabain after 4 weeks of dietary supplementation with 10, 35, or 60 mg DHA per kg body weight, compared to no supplementation (DHA10, DHA35, DHA60, and control groups, respectively). The responsiveness of contraction to different doses of ouabain (10(-7) to 10(-4) M), ouabain intoxication (at 3 X 10(-4) M), and relative changes in cardiac energy metabolism were determined using (31)P NMR in isolated perfused rat hearts. The fatty acid composition of cardiac membranes was analyzed by gas chromatography. DHA accumulation in the heart was dose-dependent (+8%, +30%, and +45% for DHA10, DHA35, and DHA60, respectively). The cardiac phosphocreatine content significantly increased at baseline in DHA35 (+45%) and DHA60 groups (+85%), and at different doses of ouabain in the DHA60 group (+73% to 98%). The maximum positive inotropy achieved at 10(-4) M ouabain was significantly increased in all DHA groups compared to control (+150%, +122.5%, and +135% for DHA10, DHA35, and DHA60, respectively), and ouabain intoxication was delayed. The increase in myocardial phosphocreatine content and the improved efficacy of ouabain on myocardial contraction without toxicity suggest the potential of GPL-DHA as a dietary supplement or ingredient for functional foods, and possibly as a co-treatment with digitalis drugs in humans.
Docosahexaenoic acid (DHA) might prevent heart failure or optimize drug treatments by improving cardiac contraction. We investigated whether DHA-enriched avian glycerophospholipids (GPL-DHA) exert cardioprotection in ouabain-treated rats after 4 weeks of dietary supplementation with 10, 35 or 60 mg DHA per kg body weight versus none (DHA10, DHA35, DHA60 and control groups, respectively). The contractile responsiveness to different doses of ouabain (10(-7) to 10(-4) M), ouabain intoxication (at 3 X 10(-4) M), and relative variations in cardiac energy metabolism were determined using (31)P NMR in isolated perfused rat hearts. The fatty acid composition of cardiac membranes was analyzed by gas chromatography. DHA accretion in the heart was dose-dependent (+8%, +30% and +45% for DHA10, DHA35 and DHA60, respectively). The cardiac phosphocreatine content significantly increased at the baseline in DHA35 (+45%) and DHA60 groups (+85%), and at the different doses of ouabain in the DHA60 group (+73% to 98%). The maximum positive inotropy achieved at 10(-4) M ouabain was significantly increased in all DHA groups versus control (+150%, +122.5% and +135% for DHA10, DHA35 and DHA60, respectively), and ouabain intoxication was delayed. The increase in myocardial phosphocreatine content and the improved efficacy of ouabain on myocardial contraction without toxicity suggest the potential of GPL-DHA as a dietary supplement or ingredient for functional food, and possibly as a co-treatment with digitalis drugs in humans.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
静脉注射哇巴因的效果在注射后立即开始，5分钟后达到最大值，持续5-7小时，然后迅速下降。
The effect of i.v.-administered ouabain starts immediately after injection, reaches a maximum after 5 min, last 5-7 hr and then rapidly declines.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
它从消化道吸收不良，口服剂量的大部分似乎被破坏。
It is poorly absorbed from alimentary tract, where much of oral dose appears to be destroyed.
Four, 7 and 10% of (3)H-ouabain had been absorbed 1, 5 and 15 hr respectively after oral administration to guinea pigs. Percentage absorbed was constant at each of 3 dose levels. ... Similar results obtained in man. ... /It/ was absorbed from GI tract of rats by passive diffusion. Absorption of im dose probably depended more on tissue-blood flow than on rates of diffusion ... 67% of iv dose was excreted in 30-min bile of rats. ... /It/ was actively transported from liver to bile, and carbon tetrachloride pretreatment of rats reduced biliary excretion by depressing this transport.
Plasma clearance of ouabain following iv admin was much faster in rat than in rabbit or dog. Levels of radioactivity in plasma, bile, and liver ... determined 20 min after iv administration ... showed that rat exhibited overall bile to plasma concentration ratio of 1500, whereas same ratio was much less for rabbit (2.9) and dog (9.3). Liver/plasma and bile/liver concentration ratios ... were ... much greater in rat (20 and 71) than in rabbit (2.5 and 1.3) or dog (3.3 and 2.7). This species variation is thought to be important factor in resistance of rat to toxic effects of ouabain relative to rabbit and dog.
Section I.Chemical Product and Company Identification Chemical Name g-Strophanthin Portland OR Ouabain Synonym C29H44O12•8H2O Chemical Formula CAS Number 630-60-4 Section II. Composition and Information on Ingredients Chemical Name CAS Number Percent (%) TLV/PEL Toxicology Data g-Strophanthin 630-60-4 ---------- Not available. Rat LD50 (intravenous) 14 mg/kg Mouse LD50 (oral) 5 mg/kg Mouse LD50 (intraperitoneal) 11 mg/kg Mouse LD50 (subcutaneous) 5 mg/kg Section III. Hazards Identification Toxic if ingested or inhaled. Avoid prolonged contact with this material. Overexposure may result in serious illness or Acute Health Effects death. Follow safe industrial hygiene practices and always wear proper protective equipment when handling this compound. Chronic Health Effects CARCINOGENIC EFFECTS : Not available. MUTAGENIC EFFECTS : Not available. TERATOGENIC EFFECTS : Not available. DEVELOPMENTAL TOXICITY: Not available. Repeated exposure to an highly toxic material may produce general deterioration of health by an accumulation in one or many human organs. Section IV. First Aid Measures Eye Contact Check for and remove any contact lenses. In case of contact, immediately flush eyes with plenty of water for at least 15 minutes. Get medical attention. Skin Contact In case of contact, immediately flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash clothing before reuse. Thoroughly clean shoes before reuse. Get medical attention immediately. If the victim is not breathing, perform mouth-to-mouth resuscitation. Loosen tight clothing such as a collar, tie, belt or Inhalation waistband. If breathing is difficult, oxygen can be administered. Seek medical attention if respiration problems do not improve. INDUCE VOMITING by sticking finger in throat. Lower the head so that the vomit will not reenter the mouth and throat. Ingestion Loosen tight clothing such as a collar, tie, belt or waistband. If the victim is not breathing, perform mouth-to-mouth resuscitation. Examine the lips and mouth to ascertain whether the tissues are damaged, a possible indication that the toxic material was ingested; the absence of such signs, however, is not conclusive. Section V. Fire and Explosion Data Not available. Flammability May be combustible at high temperature. Auto-Ignition Flammable Limits Flash Points Not available. Not available. Combustion Products These products are toxic carbon oxides (CO, CO2). Fire Hazards Not available. Explosion Hazards Risks of explosion of the product in presence of mechanical impact: Not available. Risks of explosion of the product in presence of static discharge: Not available. Fire Fighting Media SMALL FIRE: Use DRY chemical powder. LARGE FIRE: Use water spray, fog or foam. DO NOT use water jet. and Instructions Consult with local fire authorities before attempting large scale fire-fighting operations. Continued on Next Page g-Strophanthin Section VI. Accidental Release Measures Spill Cleanup Highly Toxic material. Light sensitive material. Stop leak if without risk. DO NOT get water inside container. DO NOT touch spilled material. Use water spray to reduce Instructions vapors. Prevent entry into sewers, basements or confined areas; dike if needed. Eliminate all sources of ignition. Consult federal, state, and/or local authorities for assistance on disposal. Section VII. Handling and Storage Handling and Storage HIGHLY TOXIC. LIGHT SENSITIVE. Keep locked up. Keep away from heat. Mechanical exhaust required. When not in use, tightly seal the container and store in a dry, cool place. Avoid excessive heat and light. DO NOT ingest. Do not Information breathe dust. Wear suitable protective clothing. If ingested, seek medical advice immediately and show the container or the label. Treat symptomatically and supportively. Always store away from incompatible compounds such as oxidizing agents, acids, alkalis (bases). Section VIII. Exposure Controls/Personal Protection Engineering Controls Use process enclosures, local exhaust ventilation, or other engineering controls to keep airborne levels below recommended exposure limits. If user operations generate dust, fume or mist, use ventilation to keep exposure to airborne contaminants below the exposure limit. Personal Protection Splash goggles. Lab coat. Dust respirator. Boots. Gloves. A MSHA/NIOSH approved respirator must be used to avoid inhalation of the product. Suggested protective clothing might not be sufficient; consult a specialist BEFORE handling this product. Exposure Limits Not available. Section IX. Physical and Chemical Properties Solubility Physical state @ 20°C Solid. (White, Crystalline powder.) Not available. Not available. Specific Gravity Molecular Weight 584.65 (Anh) Partition Coefficient Not available. Boiling Point Not available. Vapor Pressure Not applicable. Melting Point Not available. Vapor Density Not available. Not available. Volatility Not available. Refractive Index Critical Temperature Not available. Odor Not available. Not available. Not available. Viscosity Taste Section X. Stability and Reactivity Data This material is stable if stored under proper conditions. (See Section VII for instructions) Stability Conditions of Instability Avoid excessive heat and light. Incompatibilities Reactive with strong oxidizing agents, strong acids, strong alkalis (bases). Section XI. Toxicological Information RTECS Number RN3850000 Eye Contact. Ingestion. Inhalation. Routes of Exposure Rat LD50 (intravenous) 14 mg/kg Toxicity Data Mouse LD50 (oral) 5 mg/kg Mouse LD50 (intraperitoneal) 11 mg/kg Mouse LD50 (subcutaneous) 5 mg/kg Chronic Toxic Effects CARCINOGENIC EFFECTS : Not available. MUTAGENIC EFFECTS : Not available. TERATOGENIC EFFECTS : Not available. DEVELOPMENTAL TOXICITY: Not available. Repeated exposure to an highly toxic material may produce general deterioration of health by an accumulation in one or many human organs. Toxic if ingested or inhaled. Avoid prolonged contact with this material. Overexposure may result in serious illness or Acute Toxic Effects death. Follow safe industrial hygiene practices and always wear proper protective equipment when handling this compound. Continued on Next Page g-Strophanthin Section XII. Ecological Information Ecotoxicity Not available. Not available. Environmental Fate Section XIII. Disposal Considerations Recycle to process, if possible. Consult your local regional authorities. You may be able to dissolve or mix material with a Waste Disposal combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber system. Observe all federal, state and local regulations when disposing of the substance. Section XIV. Transport Information DOT Classification DOT CLASS 6.1: Toxic material. PIN Number Proper Shipping Name Alkaloids, solid, n.o.s. Packing Group (PG) II DOT Pictograms Section XV. Other Regulatory Information and Pictograms TSCA Chemical Inventory This compound is ON the EPA Toxic Substances Control Act (TSCA) inventory list. (EPA) WHMIS Classification On NDSL (Canada) EINECS Number (EEC) 211-139-3 EEC Risk Statements R23/24/25- Toxic by inhalation, in contact with skin and if swallowed.
