Melvin H. Heiffer

The pharmacology of radioprotectant chemicals. General pharmacology of beta-mercapto-ethylamine.

When 100 mg of beta -mercaptoethylamine is administered intravenously to the dog over a period of 5 min a characteristic set of reactions is produced. The most notable of these in the nonanesthetized dog are violent emesis, agitation frequently leading to tonic-clonic convulsions, ataxia and a characteristic swaying movement of the front portion of the body, generalized depression, loss of pain sense, severe hypotension, relative bradycardia, blood- tinged diarrhea, and a mixed stimulation and depression of respiration. Anesthesia prevents the emetic and convulsive components of the reaction but does not affect the cardiovascular changes. The agent produces a delayed, severe, prolonged hypotension. The possibility is discussed that the physiological changes produced by this agent may contribute to its radioprotective potential. 27 references. (auth)

Acute cardiovascular and autonomic effects of WR-2721: a radioprotective compound

CALDWELL, R. W., AND HEIFFER, M. H. Acute Cardiovascular Effects of WR-2721: A Radioprotective Compound. Radiat. Res. 62, 62-69 (1975). WR-2721 is a chemical which has shown much promise as a protective agent in animals exposed to ionizing radiation. Our experiments on anesthetized dogs and cats indicate that WR-2721 has little acute cardiovascular action in these animals when given intravenously in doses of 50-200 mg/kg. A total cumulative dose of 600 mg/kg within 2 hr was not lethal and, indeed, was well tolerated. Arterial blood pressure was not markedly lowered in dogs and cats given these doses. In dogs, a slight vasodilation was noted in the femoral vascular bed after intra-arterial injection. Mydriasis and watery salivation were observed in all animals. In the dog, WR-2721 (100 mg/kg) was observed to produce blockade of the bilateral carotid artery-occlusion pressor response, the pressor response to the ganglionic stimulant DMPP, and the bradycardia to vagus nerve stimulation. In the cat, WR-2721 (100 mg/kg) also blocked the contraction of the cat nictitating membrane due to stimulation of the preganglionic fibers of the superior cervical ganglion, but not the contraction seen with postganglionic fiber stimulation. Our experiments indicate that WR-2721 is a ganglionic blocking agent. It does not share this property

The Pharmacology of Radioprotective Chemicals On Some of the Effects of Beta-Mercaptoethylamine (MEA) and Cystamine in the Rat

A severe blood hypoxia and hypotension was produced in the rat by the administration of l00 mg of cystamine per kilogram. This is not the case when l25 mg of beta -mercaptoethylamine (MEA) per kilogram is administered. Therefore, it is concluded that, although blood hypoxia and hypotension may be beneficial during cystamine-induced radioprotection, they are not present or necessary for the protection afforded by MEA. (auth)

Prolongation of effects of adrenal cortical secretion by ascorbic acid; proposed mechanism of action.

Summary The influence of ascorbic acid treatment on the hematologic effects of cortisone and of ACTH was investigated. The vitamin (plus hormones) prolongs these effects beyond that in animals which receive saline + hormones. These data suggest that the circulating titer of cortical hormone is maintained for long periods by vitamin treatment. This observation is discussed in relation to previous findings, and a mechanism proposed for the relationship of ascorbic acid to pituitary-adrenal activity.

Potentiating effect of ascorbic acid on cortisone-induced gluconeogenesis.

Summary The action of ascorbic acid treatment on the gluconeogenic action of cortisone was investigated in adrenalectomized mice. The deposition of glycogen in the liver is enhanced in animals treated with ascorbic acid in addition to cortisone. This observation is discussed in relation to the action of the vitamin in preventing the activation of the pituitary-adrenal axis in animals exposed to stressors. It is suggested that the vitamin may be synergistic with cortisone in some of its actions.