Cardio-respiratory changes and mortality in the conscious rat induced by (+)- and (+/-)-anatoxin-a.

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.