Bremazocine is an agonist at kappa-opioid receptors and an antagonist at mu-opioid receptors in the guinea-pig myenteric plexus.

The agonist and antagonist activity of bremazocine at opioid receptors in the guinea-pig myenteric plexus preparation was determined in untreated tissues and in tissues in which either mu-9 or kappa-opioid receptors were blocked preferentially. After pretreatment of the tissue with beta-funaltrexamine for 90 min followed by washing out, the IC50 value of the selective mu-ligand [D-Ala2,MePhe4,Gly-ol5]enkephalin was increased 67 fold whereas the IC50 values of the selective kappa-ligand U-69,593 and of the non-selective kappa-ligand bremazocine were not significantly changed. In this experimental design bremazocine acted only on kappa-receptors. After pretreatment of the tissue with beta-chlornaltrexamine and 10 microM of the mu-ligand for 30 min followed by washout, the IC50 value of the mu-ligand was increased 2 fold whereas the IC50 value of the selective kappa-ligand was increased 32 fold and that of bremazocine 62 fold. Under these experimental conditions, it was shown that bremazocine is an antagonist against [D-Ala2,MePhe4,Gly-ol5]enkephalin at the mu-receptor (Ke = 1.6 nM). The residual agonist activity of bremazocine is at the kappa-receptor. In naive myenteric plexus preparations the mu-antagonist activity of bremazocine cannot be demonstrated because its potency at the kappa-receptor is very high. This dual action may be of importance for the responses of bremazocine in other peripheral and central tissues.