Identification of an N-acylated-^DArg-Leu-NH₂ Dipeptide as a Highly Selective Neuropeptide FF1 Receptor Antagonist That Potently Prevents Opioid-Induced Hyperalgesia

Abstract

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Multitarget μ-Opioid Receptor Agonists─Neuropeptide FF Receptor Antagonists Induce Potent Antinociception with Reduced Adverse Side Effects

“…The better affinity and antagonist activity of DP32 and DP50 at NPFFR2, as compared to NPFFR1, suggest that the NPFFR2 subtype could be a critical target for the development of OIH and analgesic tolerance. Although we and others have provided evidence that selective NPFFR1 subtype blockade significantly reduces OIH and analgesic tolerance, highly selective antagonists for NPFFR2 subtype (>100 as compared to NPFFR1) have never been described so far, thus preventing thorough in viv o evaluation of the beneficial effect of selective NPFFR2 blockade on these phenomena.…”

“…: arbitrary units. Although we 38 and others 39 have provided evidence that selective NPFFR1 subtype blockade significantly reduces OIH and analgesic tolerance, highly selective antagonists for NPFFR2 subtype (>100 as compared to NPFFR1) have never been described so far, thus preventing thorough in vivo evaluation of the beneficial effect of selective NPFFR2 blockade on these phenomena. Naltrexone-Precipitated Withdrawal Syndrome.…”

GnRHand the photoperiodic control of seasonal reproduction: Delegating the task to kisspeptin andRFRP‐3

“…The reasons for this remain unknown, and it can not be excluded that hypothalamic RFRP‐3 regulates other seasonal functions. Therefore, studies in other seasonal species, the use of more selective NPFFR2 ligands, such as GJ14, 270 RF313 271 or RF3286, 272 and the development of novel genetically modified seasonal models are required to disclose the extent of the complex physiological role(s) played by RFRP‐3 in the control of seasonal breeding.…”