Abstract
The therapeutic efficiency of Chlorpropamide was evaluated in three patients with hypodipsia and diabetes insipidus. Hitherto extraordinarily difficult management problems, the patients responded with recovery of homeostatically appropriate thirst, improved renal concentrating ability and normalization of serum tonicity. Tests of their responses to fluid loading and water restriction indicated that normotonicity was protected during treatment through wide ranges of fluid intake varying from 2.2 to 5.0 L/twenty-four hours. Over a period of one year of treatment the patients have maintained normal fluid and electrolyte homeostasis despite abandonment of the strict fluid and diet regimens previously required to prevent wide swings in tonicity. Evidence is cited in support of the tenet that the beneficial effect of the sulfonylureas at the renal level depends upon amplification of the response of the adenyl cyclase system to residually low but facultatively controlled levels of vasopressin. The reappearance of appropriate drinking behavior during chlorpropamide treatment is probably similarly mediated, being attributable to a step-up of attenuated neural discharges by an effect of the drug on nucleotide system(s) in the brain.
Published Version
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