The nociceptin/orphanin FQ receptor partial agonist sunobinop promotes non-REM sleep in rodents and patients with insomnia

Insomnia is a common disorder that poses a significant public health burden. Current treatments for insomnia primarily target aminobutyric acid or orexin signaling, but there is a need for new mechanisms to regulate sleep-wake cycles. Here, Whiteside et al investigate the potential of the nociceptin...

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Published in:The Journal of clinical investigation 2024-01, Vol.134 (1), p.1-3
Main Authors: Whiteside, Garth T, Kyle, Donald J, Kapil, Ram R, Cipriano, Alessandra, He, Ellie, Zhou, Mingyan, Shet, Manjunath S, Hummel, Michele, Knappenberger, Terri, Fukumura, Kazuya, Matsuo, Yoshiyuki, Uehira, Masahiro, Hiroyama, Shuichi, Takai, Nozomi, Willsie, Sandra K, Harris, Stephen C
Format: Article
Language:English
Subjects:
Agonists
Alcohol use
Biomedical research
Drug dosages
Health care
Human subjects
Insomnia
Latency
Nociceptin
NREM sleep
Oral administration
Orexins
Pharmacokinetics
Public health
Respiration
Sleep
Sleep and wakefulness
Sleep disorders
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Summary:Insomnia is a common disorder that poses a significant public health burden. Current treatments for insomnia primarily target aminobutyric acid or orexin signaling, but there is a need for new mechanisms to regulate sleep-wake cycles. Here, Whiteside et al investigate the potential of the nociceptin/orphanin FQ receptor (NOP) system as a treatment for insomnia. They developed a partial agonist called sunobinop and conducted various experiments to assess its pharmacology and pharmacokinetics. In rats, sunobinop decreased wakefulness and increased non-REM sleep, effects that were mediated by NOP activation. In human subjects with insomnia, sunobinop significantly improved sleep efficiency, reduced sleep latency, wake after sleep onset, and nighttime awakenings, and increased perceived sleep quality. The drug was generally well-tolerated with no serious adverse events. These findings suggest that sunobinop, as a NOP agonist, could be a promising treatment for insomnia. Further clinical studies are underway to determine the optimal effective dose.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI164303