Respiratory inhibition and hypoglycemia by biguanides and decamethylenediguanidine

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Abstract

Data are presented which support the view that the condensed diguanidines, phenethyl- and amylbiguanide, procedure hypoglycemia through a primary inhibitory effect on certain respiratory enzymes.

Succinoxidase was found to be inhibited by the two biguanide compounds and by Synthalin A. The succinic dehydrogenase complex was mildly inhibited by PEBG and Synthalin A, but not by ABG. Cytochrome c oxidation by cytochrome oxidase was inhibited by all three compounds. Synthalin A was found to be 4–6 times more potent than the biguanides in inhibiting cytochrome oxidase activity in vitro. Thus, cytochrome oxidase may be a principal site of inhibition by the biguanides and related guanidines such as Synthalin A. The relationship of the inhibition of respiration to the development of hypoglycemia is discussed.

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    These investigations were supported by grants from the National Institute of Arthritis and Metabolic Diseases, Public Health Service.

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