naloxazone and metkephamid

The selective in vivo blockade of high affinity (mu1) opioid binding sites in mice by naloxazone reduced the analgesic potency of opiates and opioid peptides, evidenced by a shift of their analgesic ED50 values. However, the extent of these shifts varied significantly between a series of opioid drugs, ranging from 12-fold for morphine to 4-fold for D-Ala2-D-Leu5-enkephalin. These findings suggested that analgesia in naloxazone-treated animals is mediated through a different subpopulation of receptors than in normal controls. Correlating these analgesic shifts for a series of opioids with their affinity for different [3H]opioid binding sites suggested an analgesic role for delta sites. Additional studies in mice with spinal transections suggested that mu1 analgesia was primarily supraspinal.

Topics: Analgesia; Animals; Binding, Competitive; Brain; Enkephalin, Methionine; Kinetics; Mice; Mice, Inbred Strains; Morphine; Naloxone; Receptors, Opioid; Spinal Cord