CARDIORESPIRATORY CHANGES AND MORTALITY IN THE CONSCIOUS RAT INDUCED BY (+)-ANATOXIN-A AND (+/-)-ANATOXIN-A
CARDIORESPIRATORY CHANGES AND MORTALITY IN THE CONSCIOUS RAT INDUCED BY (+)-ANATOXIN-A AND (+/-)-ANATOXIN-A
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DOI：
10.1016/0041-0101(92)90388-l
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发表时间：
1992-08-01
期刊：
影响因子：
2.8
通讯作者：
SIREN, AL
中科院分区：
文献类型：
--
作者：
ADEYEMO, OM;SIREN, AL
Anatoxin-a (AnTx-a) 是一种有效的烟碱胆碱能受体激动剂。通过比较 (+)-AnTx-a 和外消旋混合物 (+/-)-AnTx-a 对平均动脉血压 (BP)、心率 (HR)、血氧和二氧化碳压力（分别为 pO2 和 pCO2）、酸碱平衡 (pH) 和死亡率的影响，在清醒大鼠中研究了它们的相对效力。目前的实验表明，虽然两种形式的 AnTx-a 都会产生剂量依赖性的血压升高和心率降低，但 (+)-AnTx-a 的效力比光学非活性异构体强约 10 倍。 (+)-AnTx-a 在产生严重低氧血症方面的效力也是 (+/-)-AnTx-a 的 6 倍，在产生严重高碳酸血症并伴有严重酸中毒方面的效力是 (+/-)-AnTx-a 的 4 倍以上。 (+)-AnTx-a 的大约半数致死剂量 (LD50) 比 (+/-)-AnTx-a 低约 5 倍。我们得出的结论是，(+)-AnTx-a 比 (+/-)-AnTx-a 外消旋混合物更能引起有害的心肺变化，从而增加大鼠的死亡率。
Anatoxin-a (AnTx-a) is a potent nicotinic cholinergic receptor agonist. The relative potencies of the (+)-AnTx-a and the racemic mixture (+/-)-AnTx-a were investigated in the conscious rat by comparing their effects on mean arterial blood pressure (BP), heart rate (HR), blood oxygen and carbon dioxide pressures (pO2 and pCO2, respectively), acid-base balance (pH) and mortality. The present experiments show that while both forms of AnTx-a produce dose-dependent increases in BP and decreases in HR, (+)-AnTx-a is about 10-fold more potent than the optically inactive isomer. (+)-AnTx-a was also 6-fold more potent than (+/-)-AnTx-a in producing severe hypoxemia, and more than 4-fold as potent as the (+/-)-AnTx-a in producing significant hypercapnia accompanied with severe acidosis. The approximate median lethal dose (LD50) of (+)-AnTx-a was about 5-fold less than that of (+/-)-AnTx-a. We conclude that (+)-AnTx-a is more potent than the (+/-)-AnTx-a racemic mixture in causing detrimental cardio-respiratory changes and therefore increased mortality in the rat.