Mechanism of chlorpropamide-induced antidiuresis in man: Evidence for release of ADH and enhancement of peripheral action

The present studies confirm the antidiuretic action of chlorpropamide in overhydrated normal subjects and in addition demonstrate that chlorpropamide significantly increases urinary ADH excretion in these subjects. Chlorpropamide does not alter the excretion of exogenous ADH and it appears therefore that the drug has a central action, either by increasing release of ADH or by overcoming the inhibitory effect of water loading on the release of ADH. Three patients with severe impairment in ability to release ADH were found to have a greater increase in urine osmolality in response to infused ADH when they were treated with chlorpropamide than when they were not so treated. This augmentation of ADH effect by chlorpropamide represents a second mechanism by which chlorpropamide exerts an antidiuretic action in man. Water loaded diabetes insipidus patients on chlorpropamide treatment were found to have a significantly lesser ability to excrete a dilute urine than did normal subjects. This indicates that patients with an impaired ability to synthesize and release ADH are more responsive than normal subjects to the antidiuretic action of chlorpropamide.