Inhibition of ADH release in the rat by narcotic antagonists

The diuretic action of two new narcotic antagonists, oxilorphan and butorphanol, was studied in rats heterozygous for hereditary hypothalmic diabetes insipidus. Both drugs caused a prompt increase in urine volume and a decrease in urine osmolality with an associated decrease in urinary ADH excretion. The effects appeared to be dose related and of short duration. Tolerance to butorphanol administration was evident on repeated daily injections. The diuretic effect was not associated with alternation in creatinine excretion, but butorphanol resulted in decreased osmolal, sodium and potassium excretion. Butorphanol prevented the expected rise in urine osmolality and ADH excretion due to 31 h of dehydration. Oxilorphan did not interfere with the ability of administered ADH to cause an antidiuresis. The data indicate that these narcotic antagonists cause a diuresis by inhibiting ADH release from the neurohypophysis.