The non-protein amino acid, beta-N-methylaminoalanine (BMAA), is neurotoxic and has been implicated in the amyotrophic lateral sclerosis-Parkinsonism-dementia (ALS-PD) complex of Guam. This concept remains controversial, in part because of the lack of a convincing animal model. The neuropharmacology of BMAA is well established, but little is known of its metabolism. ... BMAA changed the distribution of taurine, glycine and serine between rat brain slices and their incubation medium; the glutamate/glutamine cycle between neurones and glia was also compromised. In model experiments BMAA reacted non-enzymatically with pyridoxal-5'-phosphate, releasing methylamine. Rat liver and kidney homogenates, but not brain homogenates, also formed methylamine and 2,3-diaminopropanoic acid when incubated with BMAA. These results provide evidence that several biochemical mechanisms are involved in the neurotoxicity of BMAA. The novel discovery that methylamine is formed from BMAA in rat liver and kidney preparations may be significant since chronic administration of methylamine to rats causes oxidative stress. The extent to which this reaction occurs in different animal species might be a decisive factor in selecting an animal model. /beta-N-methylamino-L-alanine/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
副作用
神经毒素 - 其他中枢神经系统神经毒素
Neurotoxin - Other CNS neurotoxin
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
Determination of the environmental factors involved in neurodegenerative diseases has been elusive. Methylmercury and beta-N-methylamino-L-alanine (BMAA) have both been implicated in this role. Exposure of primary cortical cultures to these compounds independently induced concentration-dependent neurotoxicity. Importantly, concentrations of BMAA (10-100 uM) that caused no toxicity alone potentiated methylmercury (3 uM) toxicity. In addition, concentrations of BMAA and methylmercury that had no effect by themselves on the main cellular antioxidant glutathione together decreased glutathione levels. Furthermore, the combined toxicity of methylmercury and BMAA was attenuated by the cell permeant form of glutathione, glutathione monoethyl ester. The results indicate a synergistic toxic effect of the environmental neurotoxins BMAA and methylmercury, and that the interaction is at the level of glutathione depletion. /beta-N-methylamino-L-alanine/
/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
来源:Hazardous Substances Data Bank (HSDB)
毒理性
解毒与急救
/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /Poisons A and B/
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
2-氨基-3-(甲基氨基)-丙酸（BMAA）是一种神经毒性、兴奋性氨基酸，通过使用和消耗苏铁植物，与在西太平洋地区高发病率的肌萎缩侧索硬化症的一个变种的发生有关。为了评估其动力学和摄取情况，BMAA（25-400 mg/kg）被急性或慢性给予大鼠，然后在不同的时间点通过气相色谱-质谱联用技术测定血浆和脑部的浓度。在单次静脉注射后，BMAA在血浆中以快速分布相（表观分布容积约为16升/千克）被清除，随后是较慢的消除相（半衰期约为1天）。大脑摄取受到低血脑屏障渗透性-表面积乘积的限制，为2至5 x 10(-5) mL/s·g。注射后8小时内脑部BMAA水平达到峰值，然后以与血浆相似的半衰期下降。在连续输注两周（100 mg/kg/天）后，稳态脑部浓度达到10至30微克/克，仅略高于血浆中的浓度。结果表明，在大剂量（大于100 mg/kg）后，BMAA可能会在大脑中达到潜在的毒性水平（即大于250微摩尔）。然而，这样的剂量比通过苏铁的饮食或药用使用的剂量要高几个数量级。
2-Amino-3-(methylamino)-propanoic acid (BMAA) is a neurotoxic, excitatory amino acid which has been linked through cycad use and consumption with the onset of a variant of amyotrophic lateral sclerosis occurring with high incidence in the western Pacific region. ... To evaluate its kinetics and uptake, BMAA (25-400 mg/kg) was administered to rats, either acutely or chronically, and then plasma and brain concentrations were determined at various times thereafter by combined gas chromatography mass spectrometry. After single dose i.v. injection, BMAA was cleared from plasma in a rapid distribution phase (Vd approximately 16 liters/kg) followed by a slower elimination phase (half life approximately 1 day). Brain uptake was limited by a low blood-brain barrier permeability-surface area product of 2 to 5 x 10(-5) mL/sed/g. Brain BMAA levels peaked within 8 hr after injection, and then declined with a t1/2 similar to that of plasma. After two weeks of continuous infusion (100 mg/kg/day), steady-state brain concentrations equalled 10 to 30 ug/g, and only moderately exceeded those in plasma. The results suggest that BMAA may reach potentially toxic levels in brain (i.e., greater than 250 uM) after large doses (greater than 100 mg/kg). However, such doses are orders of magnitude greater than those available from dietary or medicinal use of cycads.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
beta-N-甲基氨基-L-丙氨酸（BMAA）是一种神经毒性的植物氨基酸，它与西太平洋地区高发肌萎缩侧索硬化症及相关帕金森病痴呆的发病机制有关。先前的研究已经证明，BMAA可以通过静脉或口服给药进入大脑。为了研究大脑传递的动力学和机制，使用原位脑灌注技术测量了BMAA在大鼠血脑屏障的流入。发现BMAA的流入是可饱和的，最大传递速率（Vmax）为1.6 ± 0.3 x 10(-3) umol/s/g，半饱和常数（Km）为2.9 ± 0.7 mM，基于总灌注液BMAA浓度。摄取是钠独立的，并且可以通过过量的L-亮氨酸抑制，但不受L-赖氨酸、L-谷氨酸或β-甲基氨基异丁酸的影响，这表明是通过脑血管大中性氨基酸载体转移的。L-BMAA如预期那样竞争性地减少了L-[14C]亮氨酸的大脑流入。结果表明，BMAA是通过血脑屏障的大中性氨基酸载体进入大脑的，并且推测摄取可能受到影响中性氨基酸运输相同因素的影响，如饮食、代谢、疾病和年龄。
beta-N-Methylamino-L-alanine (BMAA) is a neurotoxic plant amino acid that has been implicated in the pathogenesis of the high incidence amyotrophic lateral sclerosis and related parkinsonism dementia of the western Pacific. Previous studies have demonstrated that BMAA is taken up into brain following intravenous or oral administration. To examine the kinetics and mechanism of brain transfer, BMAA influx across the blood-brain barrier was measured in rats using an in situ brain perfusion technique. BMAA influx was found to be saturable with a maximal transfer rate (Vmax) of 1.6 +/- 0.3 x 10(-3) umol/s/g and a half-saturation constant (Km) of 2.9 +/- 0.7 mM based on total perfusate BMAA concentration. Uptake was sodium independent and inhibitable by excess L-leucine, but not by L-lysine, L-glutamate, or methylaminoisobutyric acid, indicative of transfer by the cerebrovascular large neutral amino acid carrier. L-BMAA competitively reduced brain influx of L-[14C]leucine, as expected for cross-inhibition. The results demonstrate that BMAA is taken up into brain by the large neutral amino acid carrier of the blood-brain barrier and suggest that uptake may be sensitive to the same factors that affect neutral amino acid transport, such as diet, metabolism, disease, and age. /beta-N-Methylamino-L-alanine/
