The synthetic
steroid nivazol lacks three of the substituents considered to be important for
glucocorticoid activity, i.e. the 3-keto, the 11-hydroxy, and the 20-keto groups. Nevertheless, in the rat,
nivazol has the activity profile of a
glucocorticoid.
After treatment of intact female rats with
nivazol , the mean weights of the adrenals and thymus were lower than those in the vehicle-treated control group. The results were qualitatively and quantitatively similar to those obtained with
methylprednisolone. Thymolysis as well as
liver glycogen deposition were seen in adrenalectomized rats treated with
nivazol , and eosinopenia and inhibition of
carrageenan edema were noted in intact rats. In the rhesus monkey, treatment with
nivazol resulted in a marked reduction in circulating
cortisol levels and elimination of the diurnal pattern, although a dose 10 times that needed to reduce circulating
cortisol levels did not produce eosinopenia or increase fasting
blood glucose levels. Both eosinopenia and higher fasting
blood glucose levels were seen
after treatment with
methylprednisolone.
Nivazol did not prevent the
ACTH-induced increase in circulating
cortisol levels nor did it alter circulating
aldosterone levels. Therefore, suppression of
ACTH is the predominant if not the sole action of
nivazol in the primate. Preliminary results in clinical trials suggest a similar activity profile in humans. Therefore,
nivazol elicits numerous
glucocorticoid activities in the rodent, but only the inhibition of the hypothalamic-pituitary-adrenal axis was observed in the primate. It is of special interest that the inhibition of the hypothalamic-pituitary-adrenal axis occurs without altering circulating
aldosterone levels and without evidence of debilitating catabolic activity.