Kappa-opiate-induced diuresis and changes in blood pressure: demonstration of receptor stereoselectivity using (+)- and (-)-tifluadom.

(+)-Tifluadom injected i.p. produced a biphasic response of urine output: within the first hour of its administration the drug produced antidiuresis followed by a diuretic phase. In contrast, the (-) isomer produced a modest reduction in urine output as compared to the output of the saline-treated rats. In addition, (+)-tifluadom markedly reduced the output of urinary Na+ and K+. The effects of (+)-tifluadom were blocked by 7.5 mg/kg naloxone but not by 10 mg/kg of the benzodiazepine antagonist Ro 15-1788. Parallel experiments demonstrated that the i.v. administration of (+)-tifluadom to non-anesthetized rats caused a dose-related pressor response that lasted for at least 15 min. This effect of (+)-tifluadom was blocked and antagonized by naloxone. In contrast, (-)-tifluadom was either inactive on the cardiovascular system or produced short-lasting hypotension. In pentobarbital-anesthetized rats, 100 micrograms/kg (+)-tifluadom caused a precipitous hypotension that was reversed by naloxone but not by Ro 15-1788.