Chlorpromazine increases the lowered response to antidiuretic hormone in rats with lithium-induced diabetes insipidus

The interaction between chlorpromazine (CPZ) and lithium on renal concentrating ability was studied in rats fed a Li-containing diet for 8 weeks (plasma-Li 0.6-0.7 mmol/l). CPZ (15 mg/kg daily orally) reduced the polydipsia and increased the ability to concentrate the urine upon water deprivation in rats treated with lithium. CPZ also reduced systolic blood pressure, but had no effect on the glomerular filtration rate or plasma levels of arginine vasopressin (AVP) in hydrated rats treated with lithium. However, CPZ prevented the rise in plasma AVP levels observed in lithium-polyuric rats in response to dehydration. During anaesthesia CPZ partially restored the impaired anti-diuretic response to exogenous AVP in rats treated with lithium. CPZ had no influence on plasma-Li levels in rats treated with lithium. It is suggested that CPZ by unknown mechanisms interferes with the effects of lithium on the water permeability response to AVP.