Chemical Reactivity of Morphine and Morphine-6-conjugates and Their Binding to Rat Brain

抄録

By substitution reaction with nucleophilic reagents such as lithium chloride and piperidine, morphine-6-conjugates were found to be convertible easily to 6-chloro-6-deoxy-morphine and 8-piperidino-6-deoxy-Δ⁶-morphine, respectively. The reaction rates of these conjugates were roughly parallel with the analgesic activity, decreasing in the order sulfate>glucuronide≒acetate>phosphate>morphine. Furthermore, in the hope that the similar binding of morphine and its 6-conjugates to nucleophilic sites of the brain macromolecule which is closely related to the analgesic receptor might occur, the binding experiment to rat brain homogenates was conducted using morphine and morphine-6-glucuronide which is known to possess stronger analgesic activity than morphine. As the result, the 6-glucuronide showed greater affinity to rat brain but lesser extent of binding to rat liver and bovine serum albumin than morphine.