Dapiprazole, a selective alpha-1 adrenoceptor antagonist, inhibits diuresis but not polydipsia produced by amphetamine in rats.

Chronic amphetamine administration has been found to produce diuresis and polydipsia in rats. We have found that dapiprazole acutely suppresses the diuretic, but not the ingestive, effects of amphetamine. To see whether diuresis is the physiological stimulus driving amphetamine-mediated polydipsia, we injected rats daily with d,l-amphetamine and the alpha-1 adrenergic antagonist dapiprazole. Throughout 19 days of treatment, dapiprazole completely prevented the increased urine output produced by amphetamine, but did not affect the development of polydipsia. This finding rules out a renal site of the primary action for amphetamine-mediated polydipsia and proposes water and electrolyte imbalance produced by chronic amphetamine administration as a model of the polydipsia and hyponatremia that develop in some psychotic patients.