Journal
NEUROPHARMACOLOGY
Volume 151, Issue -, Pages 195-207Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2019.03.006
Keywords
Opioids; Analgesics; Drug discovery; Tolerance; Nociceptin (NOP) receptor; Bifunctional activity
Categories
Funding
- Concordia University Wisconsin
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Prolonged treatment of chronic severe pain with opioid analgesics is frought with problematic adverse effects including tolerance, dependence, and life-threatening respiratory depression. Though these effects are mediated predominately through preferential activation of mu opioid peptide (mu OP) receptors, there is an emerging appreciation that actions at kappa OP and delta OP receptors contribute to the observed pharmacologic and behavioral profile of mu OP receptor agonists and may be targeted simultaneously to afford improved analgesic effects. Recent developments have also identified the related nociceptin opioid peptide (NOP) receptor as a key modulator of the effects of mu OP receptor signaling. We review here the available literature describing OP neurotransmitter systems and highlight recent drug and probe design strategies.
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