Possible Interaction: Valproic Acid and Adrenocorticotropic Hormone

“ Valproic acid decreased moderately ACTH concentration in two patients, while following dexamethasone administration a fall in ACTH levels was observed in all three patients, the most evident in the patient with a non-invasive Nelson's adenoma.”

“Previous studies have found that bromocriptine, cyproheptadine, and valproic acid can reduce ACTH secretion in Nelson's syndrome, but none of these agents has achieved widespread use due to their failure to normalize ACTH in most patients.”

“ Sodium valproate (SV) inhibits ACTH release in response to CRH, metyrapone and substance P. We hypothesized that, if this action is GABAA‐mediated, SV should also inhibit naloxone‐stimulated ACTH release.”

“A single dose of 400 mg of MV , led to a reduction in plasma ACTH concentration only in two out of seven patients during a four-hour observation.”

“ Sodium valproate , a gamma-aminobutyric acid (GABA) agonist, was found to decrease plasma ACTH concentration in some cases of Cushing's disease and Nelson's syndrome.”

“The daily dose, 1200 mg of MV , significantly decreased plasma ACTH level at 10 p.m. compared with placebo.”

“Better results in a clinical … by the combined use of ACTH … valproic acid , which increases the amount of GABA in the brain, than by the use of ACTH alone; the combined … animal experiment using rats resulted in a more conspicuous increase in the amount of GABA in the brain.”

“They also indicate that chronic administration of sodium valproate , hence activation of central gamma-aminobutyric acid system, results in a blunting of the stimulated GH and ACTH secretion.”

“ Di-n-propylacetic acid (valproic acid) has been reported to lower plasma ACTH concentration after both acute and chronic administration of the drug.”

“It has previously been reported that sodium valproate Epilim ) lowers plasma ACTH levels in Nelson's syndrome.”

“Naloxone and valproic acid caused a decline in plasma ACTH concentrations in the patients with Nelson's syndrome, but produced no change in the patient without Nelson's syndrome.”