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.
Adeyemo
O M
OM
Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, MD 20889-4799.
Sirén
A L
AL
D000818:Animals; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000633:toxicity*; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D000087522:Cyanobacteria Toxins; D006331:Heart Diseases / Q000139:chemically induced*; D006339:Heart Rate / Q000187:drug effects; D006935:Hypercapnia / Q000139:chemically induced; D000860:Hypoxia / Q000139:chemically induced; D007928:Lethal Dose 50; D008297:Male; D008387:Marine Toxins / Q000008:administration & dosage / Q000633:toxicity*; D052998:Microcystins; D051381:Rats; D011919:Rats, Inbred Strains; D012120:Respiration Disorders / Q000139:chemically induced*; D014326:Tropanes
D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; D014326:Tropanes; C509783:anatoxin a