The mu-opioid activity of kappa-opioid receptor agonist compounds in the guinea pig ileum.

On the basis of their in vivo activity and binding affinity, nalorphine and (-)SKF 10,047 were classified as mixed agonist/antagonist compounds. However, in isolated tissue preparations without a selective antagonist to block their agonist effect, the characterization of these compounds and the determination of their antagonist activity were very difficult. Nor-binaltorphimine, a selective kappa-opioid receptor antagonist, was used in the longitudinal muscle preparations of the guinea pig ileum to block the kappa-agonist activity of nalorphine and (-)SKF 10,047. In the absence of their kappa-agonist activity, we were able to determine the mu-antagonist activity using the mu-selective agonist DAMGO ([D-Ala2,N-Me-Phe4,Gly-ol5]enkephalin). The pA2 values for nalorphine and (-)SKF 10,047 were 7.50 and 7.69, respectively.