2. Signaling Pathways
  3. GPCR/G Protein
  4. Neuropeptide FF Receptor
  5. NPFFR1 Isoform

NPFFR1

NPFFR1 (neuropeptide FF receptor 1, GPR147) is a class A G protein-coupled receptor that functions as a receptor for the RF-amide neuropeptides NPFF and NPAF and mediates neuropeptide signaling through Gi/o-dependent pathways[1][2]. Mechanistically, NPFFR1 participates in neuropeptide signaling networks that regulate nociception, opioid responsiveness, hormonal modulation, thermoregulation, and metabolic homeostasis, linking extracellular RF-amide peptides to intracellular signaling programs[3][4]. Structural studies further demonstrated that NPFFR1 and NPFFR2 share conserved RF-amide peptide recognition mechanisms while exhibiting subtype-specific determinants of ligand selectivity and G-protein coupling, providing a molecular basis for distinct biological functions[3]. In disease-relevant and pharmacological models, the NPFF system has been strongly associated with pain regulation, opioid tolerance, opioid dependence, and metabolic disorders, making NPFFR1 an important target for mechanistic studies of neuropeptide-mediated signaling[4][5]. Compared with the related isoform NPFFR2, NPFFR1 is broadly distributed throughout the central nervous system, particularly in limbic and hypothalamic regions, whereas NPFFR2 is more prominently associated with spinal nociceptive circuits, highlighting functional specialization between the receptor subtypes[6]. For experimental applications, endogenous RFamide-related peptides, including RFRP-derived ligands, activate NPFFR1, while subtype-selective antagonists have been developed to dissect NPFFR1-dependent regulation of reproduction, stress responses, anxiety-related behaviors, and opioid-associated signaling pathways[7].

NPFFR1 Related Products (4):

Cat. No. Product Name Effect Purity
  • HY-P1248
    Neuropeptide FF
    		99.35%
    Neuropeptide FF (NPFF), an octapeptide belonging to the RF-amide family of peptides, is a NPFF1 and NPFF2 receptors agonist with Ki values of 2.82 nM and 0.21 nM, respectively. Neuropeptide FF induces abstinence syndrome, exerts antiopioid and analgesic effects, releases via calcium-dependent mechanisms from rat spinal cord, regulates memory, autonomic function, and neuroendocrine function, modulates pain and opioid antinociception, reduces food intake, stimulates water intake, alters cardiovascular parameters, and shows differential activity in hypothalamic paraventricular nucleus neurons. Neuropeptide FF is present in mammalian central nervous system and periphery, with NPFF-immunoreactivity increases in rat cerebrospinal fluid during opiate tolerance, and its NPFF gene and NPFF-R2 gene are up-regulated in rat spinal cord and dorsal root ganglia during peripheral inflammation. Neuropeptide FF can be used for the research of opioid tolerance, morphine-induced analgesia, abstinence syndrome, pain, hypertension, nociception, inflammatory pain, and neuropathic pain.
  • HY-161405
    NPFF1-R antagonist 1
    		Inhibitor 99.38%
    NPFF1-R antagonist 1 (compound 8b), a piperidine analogue, is a potent neuropeptide FF (NPFF) receptor antagonist. NPFF1-R antagonist 1 is 15-fold selective for the NPFF1-R subtype, with Ki values of 211 nM and 3270 nM for NPFF1-R and NPFF2-R, respectively.
  • HY-P10395
    DP50
    		Antagonist
    DP50 is a bifunctional compound that contains an opioid receptor (MOP) agonist and a neuropeptide FF receptor (NPFFR) antagonist. DP50 can be used in analgesia-related research.
  • HY-P10394
    DP32
    		Antagonist
    DP32 is a bifunctional compound that contains an opioid receptor (MOP) agonist and a neuropeptide FF receptor (NPFFR) antagonist. DP32 can be used in analgesia-related research.