Effects of morphine and clonidine on sulphobromophthalein disposition in mice

Levels of sulphobromophthalein (BSP) in plasma and liver were elevated by the opiate, morphine, and by the alpha 2-adrenoceptor agonist, clonidine. Neither morphine, 1 mg kg-1, nor clonidine, 0.01 mg kg-1, affected BSP levels significantly. When given together at these doses, they caused BSP levels in plasma and liver to be raised. At 20 mg kg-1, the effect of morphine on BSP levels was maximal, as was that of clonidine, 1.0 mg kg-1. However, the effect of these drugs given together on plasma BSP exceeded the maximal effect of either alone. Yohimbine, an alpha 2-adrenoceptor antagonist, did not affect BSP levels, nor did the opiate antagonist, naloxone. Each of these antagonists reversed the hepatobiliary effects of its respective agonist, as shown by return of BSP levels to those of saline-treated mice. Yohimbine did not reverse morphine, nor did naloxone reverse clonidine. The additive effects of morphine and clonidine and the specificities of their respective antagonists strongly suggest the involvement of discrete receptors mediating their essentially identical hepatobiliary effects.