Pharmacological study of an irreversible partial agonist of opiate receptors, A-alpha-CAO.

A-alpha-CAO induces weak analgesia with very short duration in mice and is able to antagonize the analgesic effect of morphine (Mor) up to 3-4 days after a single injection. No tendency of dependence has been observed. It acts as a partial agonist on MVD with Ke value of 9 X 10(-9) mol/L. Its antagonist effect remains after several washes and its agonist effect cannot be reversed by naloxone (Nx), provided the incubation time or the concentration of the agent is sufficient. On isolated GPI, A-alpha-CAO is a pure agonist with IC50 of 5.7 X 10(-10) mol/L; this agonist effect cannot be removed by washing but can be reversed by Nx. On RVD and RbVD, it has antagonist effect against beta-endorphine (beta-end) and U50488H, which cannot be washed out easily, and the pA2 are 7.5 and 7.6 respectively. A-alpha-CAO also inhibits the specific binding of 3H-etorphine (3H-Etor) to the P2 fraction of the mouse brain membrane with an IC50 of 3.2 X 10(-9) mol/L. The inhibition on the high affinity binding sites of 3H-Etor remains 95% even after 6 washes.