Ultra-long antagonism of kappa opioid agonist-induced diuresis by intracisternal XXXX in monkeys.

@entity14719 @entity4596 @entity31901 @entity8539
@entity31901 ( @entity31901 ) agonists such as @entity4596 and @entity8539 are analgesics and diuretics. In monkeys, the selective @entity31901 antagonist, @entity14719 ( @entity14719 ), produces a long-lasting antagonism of the antinociceptive effects of @entity4596 but not those of @entity8539 , suggesting that @entity31901 -mediated antinociception may occur through two distinct KORs. The aim of this study was to characterize the antagonist effect of @entity14719 against the diuretic effects of @entity4596 and @entity8539 in monkeys. Urine outputs were collected over 3 h subsequent to i.m. administration of @entity31901 agonists. Both @entity4596 (0.032-1 mg/kg) and @entity8539 (0.00032-0.01 mg/kg) dose-dependently increased urine output and the diuretic effect reached a plateau at higher doses. The maximum effect of either @entity4596 or @entity8539 was approximately 15 ml/kg/3 h of urine. Pretreatment with intracisternal @entity14719 0.32 mg significantly blocked both @entity4596 (0.18 mg/kg)- and @entity8539 (0.0032 mg/kg)-induced diuresis for 20 weeks. However, the same dose of @entity14719 0.32 mg given subcutaneously was not effective. These results demonstrate that central @entity31901 mediate @entity31901 agonist-induced diuresis in monkeys. More important, this study provides functional evidence for a homogenous population of @entity31901 underlying @entity31901 -mediated diuresis and illustrates a unique pharmacological profile of @entity14719 -induced ultra-long @entity31901 antagonism in vivo.
