Effects of dantrolene on adrenal cortical function

Abstract

Adverse effects of dantrolene include abnormal liver function tests, hepatic injury, and alteration of the hepatic mixed function oxidase cytochrome P-450 system. The following study conducted in rats indicates that the effective dose of dantrolene that has been shown to decrease hepatic cytochrome P-450 also causes adrenal enlargement with a marked reduction in serum glucocorticoids. The ratio of adrenal wet weight/body weight was significantly (P < 0.05) increased following 5 days of injection with a minimum dose of 25 mg dantrolene/kg body weight. The minimum effective dose of dantrolene that significantly (P < 0.05) lowered serum glucocorticoids was 50 mg/kg body weight. Serum glucocorticoids were reduced by half following 5 days of treatment with 100 mg dantrolene/kg body weight. The levels of serum glucocorticoids were 80 per cent of control serum levels and the adrenal wet weight/body weight ratio was 85 per cent of control values following 3 days of recovery after 5 days of pre-treatment with 100 mg/kg of dantrolene. It appears that dantrolene acts in a manner similar to diphenylhydantoin to reduce adrenal glucocorticoid secretion, with a possible alteration or reduction in the negative feedback response to the pituitary and resultant enlargement of the adrenals.