Abstract
Although mannitol hexanitrate † has been used for many years for the treatment of essential hypertension and as a prophylactic against anginal attacks, few pharmacological studies are available in the literature. This paper is the first of a series designed to test this drug clinically and experimentally.
Table I shows that the 24-hour toxicity is very low when tested on 20 g mice. In another experiment, a solution of the material in triethylene glycol was given by stomach tube to 6 male rats weighing about 100 g. None of them developed any symptoms although the dosage was 1.25 g per kilogram.
In a study of chronic toxicity, 12 female rats weighing 60 g were given orally 11 mg per day of mannitol hexanitrate mixed in their diet of Purina fox chow. In addition, 6 male rats weighing 110 g received 8.5 mg in a corn oil solution daily from a medicine dropper. Nine stock animals served as controls. After 24 weeks there was no apparent effect of the drug on the rate of growth, general appearance of the rats or food intake. At autopsy they showed no gross pathological changes. Microscopic sections were made of the following tissues from 12 experimental and 5 control rats: liver, heart, spleen, kidney, and brain. These all appeared normal when stained by the H. and E. method except for moderate splenic congestion. Sections of testis and lung from four experimental rats showed no abnormalities.
Clinically it has been observed that the depressant effect of mannitol hexanitrate is more prolonged than that of other nitrate esters, e. g., glyceryl trinitrate and erythrol tetranitrate. 1 Yet the action of these compounds when injected intravenously into anesthetized cats was shown to be evanescent and similar in the blood pressure lowering, confirming the work of Herrman, et al. 2 The prolonged action of mannitol hexanitrate may depend on slowness of absorption.
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