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- W2127552242 abstract "Opium has been used for thousands of years as an analgesic and is a substance of abuse yet until recently its modes of action have remained largely unresolved. Three classical receptors for opioids have been cloned; MOP (μ), KOP (κ) and DOP (δ). Furthermore, an orphan receptor NOP has recently been identified. Endogenous agonists exist for MOP (endomorphins), KOP (dynorphins), DOP (enkephalins) and NOP (nociceptin/orphanin FQ or N/OFQ). There is substantial overlap between these Gi/o protein coupled classical opioid (MOP/KOP/DOP) and NOP systems in that activation of both results in; (1) decreased cAMP formation, (2) stimulation of K+ efflux, (3) inhibition of voltage-gated Ca2+ channels and (4) inhibition of neuronal activity. Activation of MOP/KOP/DOP produces varying degrees of analgesia with MOP agonists representing the mainstay of clinically used opioids. In addition to these functional similarities, receptor, peptide and genomic homology of the NOP–N/OFQ and MOP/KOP/DOP-opioid systems suggest a common family, supported by comparable distribution patterns in the central nervous system. At a systems level, N/OFQ produces analgesia spinally with anti-opioid actions observed supraspinally. NOP-N/OFQ pharmacology is rapidly evolving and we feel that the next class of clinically useful analgesics may target this system." @default.
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- W2127552242 date "2002-12-01" @default.
- W2127552242 modified "2023-09-27" @default.
- W2127552242 title "Molecular pharmacology of the opioid/nociceptin system" @default.
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- W2127552242 doi "https://doi.org/10.1054/cacc.2003.0426" @default.
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