Acute cognitive effects of the hypocretin receptor antagonist almorexant relative to zolpidem and placebo: a randomized clinical trial.
almorexant
cognitive dysfunction
humans
hypnotics and sedatives
psychomotor performance
zolpidem
Journal
Sleep
ISSN: 1550-9109
Titre abrégé: Sleep
Pays: United States
ID NLM: 7809084
Informations de publication
Date de publication:
13 10 2020
13 10 2020
Historique:
received:
07
10
2019
revised:
06
03
2020
pubmed:
19
4
2020
medline:
15
4
2021
entrez:
19
4
2020
Statut:
ppublish
Résumé
Hypnotic medications can adversely affect behavior during unanticipated awakenings during the night. Animals treated with the hypocretin (Hcrt) receptor antagonist almorexant (ALM) have less acute cognitive impairment compared to the GABAA receptor modulator zolpidem (ZOL). This study aimed to determine whether ALM produces less acute cognitive impairment than ZOL in human subjects. Healthy, young adult, unmedicated male and female subjects participated in a controlled trial of a single dose of ALM 100 mg (N = 48), ALM 200 mg (N = 53), ZOL 10 mg (N = 49), and placebo (PBO, N = 52). ZOL and both doses of ALM produced similar levels of subjective sleepiness and impaired the ability of subjects to remain awake in a dark, low-stimulus setting relative to PBO. For most cognitive measures, performance under ZOL was significantly worse than ALM or PBO. For tasks involving verbal memory or visual-motor coordination, ZOL impaired performance, whereas the two doses of ALM were no different than PBO. For tasks involving higher-order executive function, ZOL produced impairment in processing speed and inhibitory control, whereas the two doses of ALM were no different than PBO. Performance decrements for ALM were less than ZOL but greater than PBO for some reaction time measures. The data provide support for the hypothesis that Hcrt receptor antagonists produce less functional impairment than a benzodiazepine receptor agonist (BzRA). These observations are particularly relevant to patients treated with sedative-hypnotics who are at elevated risk for falls and other untoward events during the intended hours for sleep.
Identifiants
pubmed: 32303763
pii: 5821579
doi: 10.1093/sleep/zsaa080
pmc: PMC7551303
pii:
doi:
Substances chimiques
Acetamides
0
Hypnotics and Sedatives
0
Isoquinolines
0
Orexin Receptors
0
Orexins
0
Pyridines
0
Zolpidem
7K383OQI23
almorexant
9KCW39P2EI
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIMH NIH HHS
ID : K01 MH109871
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024131
Pays : United States
Informations de copyright
Published by Oxford University Press on behalf of Sleep Research Society (SRS) 2020.
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