nop receptors
Recently Published Documents


TOTAL DOCUMENTS

25
(FIVE YEARS 0)

H-INDEX

10
(FIVE YEARS 0)

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A192-A192
Author(s):  
M Zhou ◽  
S Harris ◽  
R Kapil ◽  
A Cipriano ◽  
E He ◽  
...  

Abstract Introduction V117957 is a recently described investigational oral, potent, and selective nociceptin/orphanin-FQ peptide (NOP) receptor partial agonist which was previously evaluated in ~200 healthy subjects. Its satisfactory safety/tolerability profile has been established with the top doses at 30mg following a single oral administration and 10mg once daily for 2 weeks. V117957 demonstrated favorable drug-like properties for insomnia treatment, including oral bioavailability, fast absorption, and rapid elimination. Methods A total of 52 patients with insomnia disorder have been evaluated in two separate randomized, double-blind, crossover, placebo-controlled sleep studies. Insomnia disorder was confirmed by screening polysomnography (PSG). All subjects received orally, for two consecutive nights, either V117957 10mg or placebo in Study #1 or 0.5, 1, 3, 6mg or placebo in Study #2. Efficacy was measured via PSG for the primary endpoint of sleep efficiency (SE) and secondary endpoints of sleep onset (latency to persistent sleep [LPS]) and maintenance (wakefulness after sleep onset [WASO]). Efficacy also was measured by patient diary (subjective sleep latency [sSL], subjective total sleep time [sTST], sWASO). Pharmacodynamics (PD) on next-day residual effects were also measured, including cognitive, psychomotor and mood effects. Results V117957 showed statistically significant greater sleep efficiency and less WASO in a dose-dependent manner (0.5-10 mg) and a statistically significant reduction in LPS at 10mg, as compared to placebo. V117957 at 0.5mg and 1mg exhibited next-day residual effects similar to placebo. At doses of 3mg or higher, V117957 showed dose-dependent next-day residual effects. V117957 was safe and well-tolerated across all doses tested with no serious adverse events, with somnolence being the most frequent treatment-emergent adverse event. No concerning laboratory findings and no clinically significant findings on vital signs and electrocardiograms have been attributed to V117957 in these subjects. Conclusion V117957 was safe and well-tolerated in patients with insomnia disorder. These results demonstrated that NOP receptors represent a novel mechanistic treatment for insomnia disorder and support continued evaluation of V117957. Support Funded by Shionogi and Imbrium Therapeutics, a subsidiary of Purdue Pharma L.P.


SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A1-A1
Author(s):  
G T Whiteside ◽  
M Hummel ◽  
T Knappenberger ◽  
S Hiroyama ◽  
T Itoh ◽  
...  

Abstract Introduction Treatments for insomnia have targeted GABA, histamine, serotonin, melatonin and orexin receptors. The nociceptin/orphanin-FQ peptide (NOP) receptor is widely expressed in the nervous system. High doses of NOP agonists administered systemically or locally into the CNS can result in sedation, however, the utility of targeting this receptor to treat insomnia has not been fully described. Methods V117957 is a recently described investigational oral, potent and selective NOP receptor partial agonist. We determined the brain Kp in whole brain and multiple sub-regions (50mg/kg) and receptor occupancy in the hypothalamus (30, 300mg/kg) via in vivo displacement using [3H]-NOP-1A. EEG/EMG were determined in rats chronically implanted with electrodes (cortex and dorsal neck muscle) and recorded via telemetry following dosing (3, 30, 300mg/kg); sleep stage was determined from visual analysis of EEG level. Sleep parameters were also assessed in NOP receptor knock-out rats (300mg/kg). The side-effect profile for V117957 was determined by functional observation battery, whole-body plethysmography, Morris water maze (MWM) (up to 600mg/kg) and conditioned place preference (CPP) assay (up to 300mg/kg). Results V117957 displayed limited distribution into the CNS but achieved a high level of receptor occupancy (75% at 30mg/kg). Administration of V117957 produced dose-dependent and statistically significant increases in non-REM sleep with a minimally efficacious dose of 30mg/kg; a coincident dose-dependent and statistically significant decrease in wakefulness and a non-dose-dependent effect on REM sleep occurred. These changes were not seen in knock-out animals demonstrating effects are via NOP receptors. At doses higher than those that increased non-REM sleep, V117957 had no effects in a functional observational battery, did not affect escape latency in MWM or produce CPP; additionally, V117957 did not affect respiratory parameters. Conclusion We conclude that activation of NOP receptors decreases wakefulness and increases non-REM sleep in rats with an improved preclinical profile compared to historical profiles of current treatments and, therefore, may represent a novel and attractive target for the treatment of insomnia. Support Funded by Shionogi and Imbrium Therapeutics, a subsidiary of Purdue Pharma L.P.


IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S13
Author(s):  
Lawrence Toll ◽  
Akihiko Ozawa ◽  
Andrea Cippitelli

2019 ◽  
Vol 44 (8) ◽  
pp. 1476-1484 ◽  
Author(s):  
Shawn M. Flynn ◽  
Phillip M. Epperly ◽  
April T. Davenport ◽  
Gerta Cami-Kobeci ◽  
Stephen M. Husbands ◽  
...  

2018 ◽  
Vol 175 (13) ◽  
pp. 2662-2675 ◽  
Author(s):  
Akihiko Ozawa ◽  
Gloria Brunori ◽  
Andrea Cippitelli ◽  
Nicholas Toll ◽  
Jennifer Schoch ◽  
...  

2017 ◽  
Vol 234 (20) ◽  
pp. 3009-3025 ◽  
Author(s):  
Juliana Almeida da Silva ◽  
Audrey Franceschi Biagioni ◽  
Rafael Carvalho Almada ◽  
Renato Leonardo de Freitas ◽  
Norberto Cysne Coimbra

Neuropeptides ◽  
2016 ◽  
Vol 57 ◽  
pp. 35-44 ◽  
Author(s):  
Aline Fassini ◽  
América A. Scopinho ◽  
Leonardo B.M. Resstel ◽  
Fernando M.A. Corrêa

NeuroImage ◽  
2014 ◽  
Vol 87 ◽  
pp. 89-95 ◽  
Author(s):  
Talakad G. Lohith ◽  
Sami S. Zoghbi ◽  
Cheryl L. Morse ◽  
Maria D. Ferraris Araneta ◽  
Vanessa N. Barth ◽  
...  

2013 ◽  
Vol 14 (10) ◽  
pp. 1203-1209 ◽  
Author(s):  
Marta Sobczak ◽  
Maciej Saaga ◽  
Martin Storr ◽  
Jakub Fichna

Sign in / Sign up

Export Citation Format

Share Document