K.K. Chen

Toxicity of Nicotinic Acid

Summary Nicotinic acid is at least several hundred times less toxic in mice, rats, and guinea pigs than nicotine. Nicotinic acid is devoid of action upon the autonomic ganglia. Nevertheless, repeated administration of large doses, 2 gm. daily, in dogs has resulted in poisoning and deaths.

Hypoglycemic action of sulfanilamido-cyclopropylthiazole in rabbits, and its reversal by alloxan.

Summary 1. 2-Sulfanilamido-5-cyclopropyl-1,3,4-thiadiazole, like other sulfonamides, has a chemotherapeutic action against certain pathogenic bacteria. It has a low toxicity. There is no evidence of conjugation as. judged by blood examination. 2. When given to normal rabbits, the substance uniformly causes hypoglycemia-with or without a slight initial rise of blood sugar. On the other hand, in diabetic rabbits induced by alloxan, it produces a definite rise of blood sugar.

Passage of Sulfanilamide from Mother to Fetus

Summary Sulfanilamide when given by mouth in pregnant rabbits has been shown to pass from the maternal to the fetal circulation. The acetylated form is relatively lower in the fetal blood than in the maternal blood. Sulfanilamide can be also detected in the amniotic fluid.

Renal clearance of erythromycin.

Summary The renal clearance of erythromycin is slightly less than the glomerular filtration rate in dogs. Benemid appears to inhibit the reabsorption of erythromycin by the renal tubules.

Ultra-short-acting thiobarbituric acids.

Summary Four N-methyl thiobarbituric acids have been studied and compared with sodium 5-allyl-5-(1-methylbutyl) thiobarbitu-rate and thiopental in rats, rabbits, cats, and dogs. They are all potent anesthetics by intravenous injection. The N-methylated derivatives, in an observed AD60 duration of anesthetic and hypnotic action than the 2 non-methylated compounds. When one-half of AD50 is intravenously injected at hourly intervals, all 4 N-methyl-substituted barbiturates show less cumulative action than sodium 5-allyl-5-(1-methylbutyl) thiobarbiturate and still less than thiopental. In anesthetized cats, 2 of the N-methyl barbiturates produce less hiccup, sneezing, and coughing than sodium 5-allyl-5-(1-methylbutyl) thiobarbiturate and thiopental, while the 2 others are free from such effects. Like all barbiturates, the 4 N-methylated compounds, when injected intravenously in anesthetized dogs, lower the blood pressure and depress respiration. They do not inhibit the vagal response in these preparations. They induce slight hypothermia and tachycardia in dogs following an AD50 of each product. The authors are indebted to Misses Eva Sommermeyer and Marion Ellaby, and to Messrs. William R. Gibson. Wallace C. Wood, James E. Waddell, E. Brown Robbins, and Lester Le Compte for their invaluable assistance in this work.

Parotoid secretions of Indonesian toads.

A preliminary study of the parotoid secretions of Bufo melanostictus and B. asper shows that a methanol extract is rich in digitalis-like bodies (bufo-dienolides) and that an acid extract contains indolethylamine derivatives.

Comparison of cardiac action of bufalin, cinobufotalin, and telocinobufagin with cinobufagin.

Summary The cardiac activity of bufalin, cinobufotalin, telocinobufagin and cinobufagin has been compared. They all have a digitalis-like action. In etherized cats the order of activity from high to low is telecinobufagin > bufalin > cinobufotalin = cinobufagin.

Intestinal absorption of cardiac steroids.

Summary 1. Six cardiotonic steroids—digitoxin, lanatoside E, acetyl strophanthidin, ouabain, bufalin and bovoside A—have been compared with reference to intestinal absorption in dogs with a chronic jejunal loop. 2. Because of the dominance of vomiting before electrocardiographic changes took place the median emetic dose was estimated after intravenous and intrajejunal injections in order to appraise the absorbability of each steroid from the intestine. 3. In the dog digitoxin and acetyl strophanthidin were more easily absorbed than lanatoside E and bufalin. Ouabain was least absorbed—less than 5%. Although bovoside easily crossed the intestinal membrane it produced persistent loss of appetite resulting in death.

Effect of Cyanide Poisoning on the Central Nervous System of Rats and Dogs.

Summary 1. Prolonged cyanide poisoning in rats may cause cerebral changes in 10% of the animals. 2. Daily injection of potassium thiocyanate similarly results in brain injury in 10% of rats. 3. In the rat continuous administration of sodium nitrite does not produce lesions in the central nervous system. 4. In dogs cyanide poisoning with or without the nitrite-thiosulfate therapy does not induce abnormal behavior. When they die from the poisoning, their brains usually show a normal appearance.

Action of 3-Acetyl-Strophanthidin in Isolated Mammalian Heart.∗

Summary In the failing heart-lung preparation of the dog, 3-acetyl-strophanthidin has been found to produce a positive inotropic effect comparable to that produced by ouabain