Abstract
A derivative of symmetrical triazine, 2-amino-4-(p-chloroanilino)-s-triazine (chloroazanil), has been found to inhibit markedly the glycogenic and, to a lesser extent, the myotrophic actions of certain steroids. It has not been possible to inhibit the actions of all steroids nor all effects of any one steroid with chlorazanil. It was ineffective in antagonizing the estrogenic activity of estradiol and did not suppress the anti-inflammatory response to hydrocortisone, a steroid whose glycogenic activity was inhibited. The androgenic responses to norethandrolone and testosterone were, for the most part, not significantly affected. In none of these assays was chlorazanil found to have any significant effect in the absence of administered steroid.
Evidence is presented which suggests the inhibition of corticoid-induced deposition of hepatic glycogen is competitive and reversible. Since chlorazanil also inhibits the hepatic accumulation of amino acids produced by administration of hydrocortisone but not the uterine uptake of amino acids resulting from estrogen administration it has been proposed that this effect may have some bearing on its antagonism of the steroid-induced glycogenic response.
On the basis of the evidence obtained in these studies it appears that chlorazanil interferes with the effects of steroids at their peripheral sites of action. This compound is unique in that it lacks the steroid configuration present in the previously reported peripheral inhibitors of adrenocortical activity.
Footnotes
- Received February 15, 1960.