The mechanism of the antidiuretic action of chlorpropamide was studied in 13 patients with vasopressin-sensitive diabetes insipidus (DI) and in 9 normal water loaded subjects. An antidiuresis occurred in 10 of 13 patients and in all the normal subjects. A significant positive correlation was found between the ability of the patients to reduce the free water clearance (CH2O) in response to water deprivation and the ability to reduce the CH2O in response to subsequent chlorpropamide treatment. Both ethanol and water loading were able to overcome the chlorpropamide-induced antidiuresis. Water deprivation while the patients were receiving chlorpropamide resulted in a further increase in urine concentration. The data indicate that, for chlorpropamide to be able to produce an antidiuresis, some low level of endogenous antidiuretic hormone (ADH) must be present. The observations can best be explained by the hypothesis that chlorpropamide is capable of potentiating the action of low, submaximal levels of endogenous ADH to result in an enhanced antidiuretic effect. No evidence of a direct ADH-like action of chlorpropamide could be found. Since the ability to respond to the drug appears to depend on the presence of residual ADH releasing capacity of the neurohypophyseal system, the rsponse to water deprivation may serve as a useful test to predict which patients are most likely to be benefited by treatment with chlorpropamide.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical