Effects of opiates on urine output in the water-loaded rat and reversal by beta-funaltrexamine.

The effects of several mu and kappa opioid receptor agonists on urinary excretion were examined in the water-loaded rat. Mu agonists induced anti-diuresis whereas kappa agonists caused diuresis. Furthermore, high efficacy kappa agonists eg. U50, 488H and tifluadom, produced marked diuretic effects, whereas kappa partial agonists eg. nalorphine, produced low maximum diuresis. Compounds having activity at both mu and kappa receptors eg. ethylketocyclazocine(EKC) and MR2034, produced a biphasic effect, an initial anti-diuretic effect followed by a more sustained diuretic effect. The irreversible mu receptor antagonist, beta-funaltrexamine (beta-FNA) antagonized the anti-diuretic effects elicited by fentanyl, pentazocine and buprenorphine and the initial anti-diuretic effect induced by EKC but did not inhibit the diuretic effects induced by U50, 488H and EKC. Thus, the use of beta-FNA in the water-loaded rat provides us with a valuable in vivo test which differentiates both mixed and selective opioid receptor agonists.