Nociceptin receptor antagonist

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Our current studies have suggested that neuro-modulations mediated by the novel bioactive peptide named nociceptin or orphaninFQ regulate several signal-transmission pathways including pain, learning and memory and hearing. Based on our results, aims of this collaborative study were (i) attempt to identify chemical compounds acting antagonists for the nociceptin receptor, (ii) examination of such compounds as potent analgesics or memory stimulants in the whole animal level, and further (iii) analysis of physiological roles of neuro-modulations by the nociceptin system.Members in our collaborative team successfully found that chemical compounds, NalBenzH and J-113397, act as antagonists selectively for the nociceptin receptor. In our preliminary study comparing pharmacological responses of the compounds between wild-typec mice and mutant mice lacking the nociceptin receptor, they seemed to produce weak analgesic effects. However, to examine the possibility that they can be potent analgesics for broad- ranged pains or memory stimulants, we need to plan further animal-level studies. On the other hand, our collaborative studies have clarified the expression patterns of both the nociceptin precursor protein and nociceptin receptor in the central nervous system, the modulation of synaptic transmission by nociceptin in the dorsal horn of the spinal cord, the role of the nociceptin system during acquirement of morphine tolerance and dependence, and the nociceptin-mediated regulation of substanceP-induced pain responses.