Higenamine as a Potential Pharmacologic Stress Agent in the Detection of Coronary Artery Disease

Myocardial perfusion imaging (MPI) is valuable for the diagnosis, prognosis, and management of coronary artery disease (CAD). The most commonly used pharmacologic stress agents at present are vasodilators and adrenergic agents. However, these agents have contraindications and may cause adverse effects in some patients. Thus, other stress agents feasible for more patients are required. Higenamine (HG) is a β-adrenergic receptor agonist currently approved for clinical trials as a stress agent for myocardial infarction. It also has a promising value in MPI for the detection of CAD in preclinical and clinical studies. This review summarizes the application of HG on MPI, including its mechanism of action, stress protocol, efficacy, and safety.     

RP-HPLC法测定莲子心提取物中去甲乌药碱的含量

目的建立测定莲子心提取物中去甲乌药碱的HPLC分析方法。方法色谱柱为Intersil ODS-3C18(150mm×4.6mm,5μm);流动相为乙腈-水-磷酸(450∶700∶1,其中含有4.6g十二烷基硫酸钠);检测波长为284nm;进样量为10μL;体积流量为1.0mL·min-1;柱温30℃。结果去甲乌药碱的线性范围为32.92¹64.6μg·mL-1,r=0.999 9(n=5),平均回收率为98.0%,RSD为0.51%。结论该方法简单、准确、重复性好,可用于莲子心提取物中去甲乌药碱的定量测定。     

去甲乌药碱对离体豚鼠心房生理特性的影响

去甲乌药碱对离体豚鼠心房具有加强收缩力,缩短功能不应期,提高兴奋性和自律性等作用,但其效能低于异丙肾下腺素。普萘洛尔可使去甲乌药碱加速右心房自发节律的量效曲线平行右移,最大反应不变。实验还发现,去甲乌药碱可在一定程度上增强由增频电刺激所致正性阶梯现象。提示去甲乌药碱可能为β受体的部分激动剂,其增强心肌收缩力的作用似与促进Ca~(2+)的跨膜内流有关。     

去甲乌药碱对家兔肾机能的影响

去甲乌药碱恒速输注每分5μg/kg,10μg/kg能明显降低家兔肾血流量。5μg/kg输注至30分钟,尿中钠排泄减少50％,而对尿量和钾的排泄无明显影响。10μg/kg输注15分钟,使乌拉坦或戊巴比妥钠麻醉,不同水负荷量家兔的尿量和钠排泄明显降低,对钾的排泄无明显影响。     

HPLC法测定去甲乌药碱的含量

目的:改进去甲乌药碱原料药的HPLC测定方法.方法:采用Alltech公司Apollo Phenyl色谱柱(150mm×4.6mm,5μm),以0.05mo1·mL-1磷酸盐缓冲液(pH 3.0)-乙腈(90:10)为流动相,流速1.0mL·min-1,紫外检测波长284nm.结果:去甲乌药碱在0.01～0.50mg·mL-1范围内线性关系良好(r=0.999 9),最低检测限为0.5ng,日内RSD为0.99%,日间RSD为0.36%,相关杂质与去甲乌药碱分离良好.结论:该方法专属性强,简便快速,结果准确,可用作去甲乌药碱原料药的含量测定.     

Analysis for higenamine in urine by means of ultra‐high‐performance liquid chromatography–tandem mass spectrometry: Interpretation of results

Higenamine (Norcoclaurine) is a very popular substance in Chinese medicine and is present in many plants. The substance may be also found in supplements or nutrients, consumption of which may result in violation of anti‐doping rules. Higenamine is prohibited in sport at all times and included in Class S3 (β‐2‐agonists) of the World Anti‐Doping Agency (WADA) 2017 Prohibited List. The presence of higenamine in urine samples at concentrations greater than or equal to 10 ng/mL constitutes an adverse analytical finding (AAF). This work presents a new metabolite of higenamine in urine sample which was identified by means of ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). Samples were prepared according to 2 protocols – a Dilute and Shoot (DaS) approach and a method involving acid hydrolysis and double liquid‐liquid extraction (LLE). To meet the requirements typical for a confirmatory analysis, the screening procedure was further developed. In samples prepared by the DaS method, 2 peaks were observed; the earlier one was specific for higenamine and the later one unknown. MS scan analysis showed mass about 80 Da higher than that of higenamine. In turn, in samples prepared in accordance with the protocol involving hydrolysis, an increase in the area under peak for higenamine was observed, while the second peak was absent. It seems that the described strategy of detection of higenamine in urine avoids false negative results.     

基于生物大数据库分析并验证附子去甲乌药碱抗肿瘤潜在作用机制

目的?以附子主要活性成分之一去甲乌药碱为代表,探究附子治疗肿瘤的作用及其可能的机制。方法?利用预测分析工具BATMAN-TCM及多种生物数据库预测去甲乌药碱调控肿瘤发生发展的可能机制;并通过体内外实验进行效应及机制的验证。结果?数据库分析显示,去甲乌药碱可能直接调控肿瘤细胞增殖、凋亡,或通过影响心脏功能而间接影响肿瘤发生发展;动物实验表明,去甲乌药碱可显著减小结肠癌皮下移植瘤的体积（P<0.05）,促进瘤组织中肿瘤细胞的凋亡,并能显著提高结肠癌模型裸鼠体内心钠肽（ANP）水平（P<0.01）,但细胞实验发现去甲乌药碱对肿瘤细胞无直接杀伤作用。结论?附子主要活性成分之一去甲乌药碱可抑制结肠癌皮下移植瘤的生长,诱导其凋亡,从而发挥抗肿瘤作用,其机制可能与促进心脏肽类激素ANP的释放有关,可为中医临床使用附子治疗恶性肿瘤提供一定的理论依据,但附子的毒性与抗肿瘤的关系还有待进一步研究。      

盐酸去甲乌药碱心肌负荷试验对心率、血压、心肌耗氧量的影响

目的:探讨盐酸去甲乌药碱负荷试验心肌灌注显像患者心率、血压、心肌耗氧量(收缩压×心率)变化及其机理。方法:研究对象接受盐酸去甲乌药碱注射液药物负荷试验,在负荷药物输注前、0.5、1.0、2.0、4.0μg.kg-1.min-1剂量级输注过程中第3分钟、终止输注用药后第5分钟和第10分钟分别记录心率、血压、计算心肌耗氧量的数值,并与基础值进行比较。结果:静脉注射盐酸去甲乌药碱后,患者心率明显增加,最大增加23次/min(t=9.950,P<0.01),心肌耗氧量明显增加,最大增加量为3 400 mL.min-1(t=8.333,P<0.01),舒张压轻度降低,最大变化6 mmHg(t=4.895,P<0.01),收缩压无明显变化,最大增加3mmHg(t=1.633,P=0.107)。结论:盐酸去甲乌药碱增加患者心率和心肌耗氧量,起到心肌负荷作用,对血压影响不大,其有望成为临床较为安全的新型心脏负荷试验药物。     

Biphasic tracheal relaxation induced by higenamine and nantenine from Nandina domestica Thunberg

We compared the effects of the extract from fruits of Nandina domestica Thunberg (NDE) and its constituents, higenamine and nantenine, on contractile responses in isolated guinea-pig trachea. NDE (1 mg/ml) caused biphasic relaxation of the trachea precontracted with high-K(+) stimulation: the fast component was blocked by propranolol and mimicked by higenamine; and the slow was resistant to propranolol and mimicked by nantenine. Ca(2+)-induced contraction under high-K(+) stimulation was antagonized by nantenine or NDE + propranolol. These results suggest that NDE relaxes the trachea quickly through β-adrenoceptor stimulation by higenamine and slowly through Ca(2+) antagonism by nantenine.     

去甲乌药碱对心血管系统的影响

乌头属在祖国传统医药中长期用作强心药物 ,去甲乌药碱是乌头根茎中分离出的一种生物碱 ,对心血管系统具有多方面的作用。对大鼠离体心房具有正性肌力和正时性作用 ,可以松弛大动脉 ,抑制血小板聚集 ,具有抗血栓作用 ,能够抑制LPS诱导的NO产物和iNOSmRNA的表达。去甲乌药碱对动物实验性DIC具有改善作用。