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Journal of Pharmacology And Experimental Therapeutics, Vol. 74, Issue 1, 75-82, 1942
Copyright © 1942 by American Society for Pharmacology and Experimental Therapeutics

SOME TOXICOLOGICAL AND PHARMACOLOGICAL PROPERTIES OF GRAMICIDIN, TYROCIDINE AND TYROTHRICIN

HARRY J. ROBINSON 1 and HANS MOLITOR 1

1 From the Merck Institute for Therapeutic Research, Rahway, New Jersey

1. The acute, peroral, intraperitoneal and intravenous toxicity of tyrothricin, gramicidin and tyrocidine was determined in mice and rats. None of the compounds was toxic when given by mouth. Upon parenteral administration all proved definitely toxic, gramicidin and tyrothricin considerably more so than tyrocidine.

2. Daily parenteral administration of 2 mgm. of gramicidin or tyrothricin per kilogram to dogs caused death within 2-8 days. During this period the dogs lost their appetite and weight and secreted excessive amounts of saliva. Their red blood counts dropped in some cases from 6,000,000 to 3,500,000 per c.mm.

3. In isolated organs as well as in situ, tyrocidine produced greater pharmacological changes than tyrothricin or gramicidin, possibly due to its greater solubility in water.

4. None of the drugs has a pronounced specific effect on the respiratory or circulatory system. Large single doses are usually tolerated without any marked effect, while repeated administrations even of small doses cause a fall of blood pressure and impairment of respiration. With lethal doses the respiration stops shortly before the heart.

5. Concentrations of gramicidin suspensions up to 0.5 per cent are not irritating upon instillation into the conjunctival sacs of rabbits. However, application of the dried material produces marked conjunctival irritation and a long-persisting opaqueness of the cornea. When injected subcutaneously or intradermally the preparations remain unabsorbed for a long period of time.

Submitted on October 8, 1941




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Copyright © 1942 by the American Society for Pharmacology and Experimental Therapeutics.