THE INFLUENCE OF DIPHENYLHYDANTOIN AND CARBAMAZEPINE ON THE CIRCADIAN RHYTHM OF FREE URINARY CORTICOIDS AND ON THE SUPPRESSIBILITY OF THE BASAL AND THE "IMPULSIVE" ACTIVITY BY DEXAMETHASONE

Abstract

ABSTRACT In eight normal volunteers the circadian rhythm of cortisol was established by the determination of free urinary corticoids in 2 h urine samples by the competitive protein binding method. After two control days dexamethasone was infused between 10 p. m. and 4 a. m. in doses between 50 and 400 μg/h. These experiments were repeated after pre-treatment with 400 mg diphenylhydantion/day for one week and again after pre-treatment with 800 mg carbamazepine/day. Under the influence of these anti-convulsant drugs the circadian rhythm of free urinary corticoids was still present but showed more irregularities and sometimes additional peaks in the course of the day. The 24 h excretion values, the peak and the nadir values and the time of the morning peaks were not significantly different from the control days. The degree of suppression by dexamethasone was dose related both with and without the application of the anti-convulsants but under the influence of both these drugs comparable effects could only be achieved by 2 to 4 fold higher doses of dexamethasone. The suppression of basal and impulsive cortisol activities was inhibited in a similar way. According to these results it can be assumed that the anti-convulsants interfere with the feedback mechanism by decreasing the sensitivity of the central nervous system to changes in plasma glucocorticoid concentrations. An intact feedback mechanism does not seem to be an essential condition for the circadian rhythm.