NOP Receptor Ligands and Parkinson’s Disease

  • Daniela Mercatelli
  • Clarissa Anna Pisanò
  • Salvatore Novello
  • Michele MorariEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 254)


Nociceptin/Orphanin FQ (N/OFQ) and its NOP receptor are highly expressed in motor areas of the rodent, nonhuman, and human primate brain, such as primary motor cortex, thalamus, globus pallidus, striatum, and substantia nigra. Endogenous N/OFQ negatively regulates motor behavior and dopamine transmission through NOP receptors expressed by dopaminergic neurons of the substantia nigra compacta. Consistent with the existence of an N/OFQ tone over dopaminergic transmission, blockade of NOP receptor antagonists increases striatal dopamine release. In this chapter, we will review the evidence linking the N/OFQ-NOP receptor system to Parkinson’s disease (PD). We will first discuss data showing that the central N/OFQ-NOP receptor system undergoes plastic changes in different basal ganglia nuclei following dopamine depletion. Then we will show that NOP receptor antagonists relieve motor deficits in different rodent and nonhuman primate models of PD. Mechanistically, NOP receptor blockade in substantia nigra reticulata results in rebalancing of the inhibitory GABAergic and excitatory glutamatergic inputs impinging on nigro-thalamic GABAergic neurons, leading to thalamic disinhibition. We will also present data showing that, in addition to motor symptoms, N/OFQ also plays a role in the parkinsonian neurodegeneration. In fact, NOP receptor antagonists possess neuroprotective/neurorescue properties in in vitro and in vivo models of PD.


Compound 24 J-113397 L-DOPA Nociceptin/Orphanin FQ NOP Parkinson’s Disease SB-612111 Trap-101 


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Daniela Mercatelli
    • 1
  • Clarissa Anna Pisanò
    • 1
  • Salvatore Novello
    • 1
  • Michele Morari
    • 1
    Email author
  1. 1.Department of Medical Sciences, Section of Pharmacology, and National Institute of NeuroscienceUniversity of FerraraFerraraItaly

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