2-13-Orphanin FQ (swine),N-[(2S)-2-amino-3-phenylpropyl]-13-L-lysinamide-

Orphanin FQ, also known as Nociceptin, is a neuropeptide that has been the subject of extensive research due to its structural similarity to opioid peptides and its unique role in the nervous system. Unlike traditional opioids, Orphanin FQ does not bind to opioid receptors, suggesting a distinct mechanism of action. This peptide has been implicated in a variety of physiological processes, including the modulation of pain, stress responses, and gastrointestinal functions. The development of analogs such as [Arg14, Lys15] nociceptin/orphanin FQ has provided further insights into the potential therapeutic applications of this peptide system.

The mechanism of action of Orphanin FQ and its analogs involves the activation of the NOP receptor, a G protein-coupled receptor that is part of the opioid receptor family. The NOP receptor is widely distributed in the central nervous system and peripheral tissues, where it mediates various biological effects. The analog [Arg14, Lys15] nociceptin/orphanin FQ has been shown to be a highly potent agonist at the NOP receptor, exhibiting greater potency and efficacy than the natural ligand Orphanin FQ itself. In vitro studies have demonstrated that this analog can significantly decrease KCl-evoked amylase secretion from isolated pancreatic lobules of the guinea pig, indicating an inhibitory effect on exocrine pancreatic function mediated by pancreatic NOP receptors1. In vivo, the analog mimics the effects of Orphanin FQ, delaying gastric emptying, increasing colonic propulsion time, and decreasing gastric acid secretion in rats when administered intracerebroventricularly1. These effects are modulated by the selective NOP receptor antagonist UFP-101, which decreases the efficacy of [Arg14, Lys15] nociceptin/orphanin FQ, confirming the role of NOP receptors in these processes1.

Gastrointestinal Function

The NOP receptor system, modulated by Orphanin FQ and its analogs, plays a significant role in gastrointestinal functions. The analog [Arg14, Lys15] nociceptin/orphanin FQ has been shown to inhibit gut motor and secretory functions in vivo. It induces a delay in gastric emptying, an increase in colonic expulsion time, and a decrease in gastric acid secretion, suggesting potential applications in the treatment of gastrointestinal disorders where such modulation is beneficial1.

Stress and Anxiety

In the field of neuropsychiatry, Orphanin FQ has been identified as an anxiolytic agent capable of attenuating behavioral responses to stress. Studies have shown that Orphanin FQ can reduce anxiety states in animals across various behavioral paradigms, such as light-dark preference, elevated plus-maze, and exploratory behavior in unfamiliar environments. These anxiolytic-like effects are observed at low, nonsedating doses, indicating that Orphanin FQ acts as an endogenous regulator of acute anxiety responses. This suggests potential therapeutic applications for Orphanin FQ and its analogs in the management of anxiety and stress-related disorders2.