Sleep Deprivation

PUBLICATIONS

Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia

2021-11-25

 

 

 

 

 

 

 

Abstract

Dual orexin receptor antagonists (DORAs) represent a novel type of sleep medication that provide an alternative to the traditionally used positive allosteric gamma-aminobutyric acid (GABA)-A receptor modulators. Daridorexant is a new DORA that exhibited in phase 3 trials in insomnia not only a beneficial effect on sleep variables, measured objectively and assessed subjectively, but also an improvement in daytime functioning. Daridorexant was discovered through a tailored research program aimed at identifying an optimized sleep-promoting molecule with pharmacokinetic properties appropriate for covering the whole night while avoiding next-morning residual activity at efficacious doses. By specific binding to both orexin receptors, daridorexant inhibits the actions of the wake-promoting orexin (also called hypocretin) neuropeptides. This mechanism avoids a more widespread inhibition of neuronal pathways and associated side effects that are intrinsic to positive allosteric GABA-A receptor modulators. Here, we review the general pharmacology of daridorexant, based on nonclinical pharmacology studies of daridorexant, unpublished or already described, or based on work with other DORAs. Some unique features of daridorexant will be highlighted, such as the promotion of natural and surmountable sleep, the preservation of memory and cognition, the absence of tolerance development or risk of physical dependence, and how it can benefit daytime functioning.

 

read more: https://link.springer.com/article/10.1007/s00213-021-05954-0

 

Publications related to Autism in Mice

2021-11-30

 

TSHZ3 deletion causes an autism syndrome and defects in cortical projection neurons

Xavier Caubit, Paolo Gubellini, Joris Andrieux, Pierre L.Roubertoux, Mehdi Metwaly, Bernard Jacq, Ahmed Fatmi, Laurence Had-Aissouni, Kenneth Y Kwan, Pascal Salin, Michèle Carlier, Agne Lieden, Eva Rudd, Marwan Shinawi, Catherine Vincent-Delorme,Jean Marie Cuisset, Marie-Pierre Lemaitre, Fatimetou Abderrehamane, Bénedicte Duban, Jean-françois Lemaitre, Adrian S Woolf, Detlef Bockenhauer, Dany Severac, Emeric Dubois, Ying Zhu, Nenad Sestan, Alistair N Garatt, Goff Lydia Kerkerian - Le, Laurant Fasano

Nature Genetics - 26 Sept. 2016   DOI : 10.1038/ng.3681

 

 

Elsa Pittaras, Damien Colas, Bayara Chuluun, Giancarlo Allocca, Craig Heller.

(2021)Enhancing sleep after training improves memory in down syndrome model mice

In Sleep.

DOI: 10.1093/sleep/zsab247