Almorexant is a potent and competitive dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist with Ki values of 1.3 and 0.17 nM for OX1 and OX2, respectively.
Almorexant/阿莫伦特 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Tg2576 mice
Human APP transgenic mice
Intracerebroventricular injection
13.9 nmole/hr
24 hours
Suppressed ISF Aβ levels and abolished the natural diurnal variation of Aβ
Science. 2009 Nov 13;326(5955):1005-7
Mice
Grm2-Cre mice
Intraperitoneal injection
30 mg/kg
Single dose
Almorexant significantly reversed the sleep fragmentation in LHb-TeLC mice, reducing wake time and increasing NREM sleep time, but had no significant effect on REM sleep time.
Curr Biol. 2018 Feb 19;28(4):580-587.e5
Sprague-Dawley rats
Rats implanted for EEG/EMG recording
Oral
100 mg/kg
Single dose, observed for 90 minutes
To compare the effects of ALM and ZOL on the functional activation of wake-promoting systems at doses equipotent for sleep induction. Results showed that ALM is permissive for the activation of wake-promoting neurons during forced wakefulness, whereas ZOL inhibits this activation.
Neuropsychopharmacology. 2016 Mar;41(4):1144-55
Wistar rats
Accelerating rotating rod (rotarod) and forepaw grip strength tests
Oral
30, 100, 300 mg/kg
Single administration, testing lasted for 2.5 hours
To evaluate the effects of Almorexant alone or in combination with ethanol on motor performance in rats. Results showed that Almorexant alone did not affect rotarod performance or grip strength, and its combination with ethanol did not further reduce performance or grip strength.
Neuropsychopharmacology. 2011 Mar;36(4):848-56
BALB/c mice
Unpredictable chronic mild stress (UCMS) model
Oral
100 mg/kg/day
Once daily for 7 weeks
To evaluate the effects of Almorexant on UCMS-induced behavioral and physiological changes. Results showed that Almorexant reversed UCMS-induced reductions in weight gain, increased aggression, increased despair behavior, and increased anxiety behavior. Additionally, Almorexant restored UCMS-induced disruption of HPA axis negative feedback regulation.
Neuropsychopharmacology. 2012 Sep;37(10):2210-21
Rats
Post-traumatic stress disorder (PTSD) animal model
Intraperitoneal injection
150 mg/kg
Single dose, 30 minutes before exposure to predator-scent stress (PSS)
To evaluate the effects of Almorexant on behavioral responses following PSS exposure, results showed that rats treated with Almorexant displayed a higher prevalence of the PTSD phenotype.
Transl Psychiatry. 2020 Jan 21;10(1):10
Mice
Narcolepsy model
Intraperitoneal injection
30, 100, 300 mg/kg
Once every 3 days, lasting 12 hours
To evaluate the hypnotic and cataplexy-inducing efficacy of a Hcrt antagonist in an animal model with low Hcrt tone and compare the ALM efficacy profile in the disease model to that produced in wild-type (WT) control animals. ALM exacerbated cataplexy in TG mice and increased nonrapid eye movement sleep with heightened sleep/wake fragmentation in both genotypes. ALM showed greater hypnotic potency in WT mice than in TG mice. The 100 mg/kg dose conferred maximal promotion of cataplexy in TG mice and maximal promotion of REM sleep in WT mice. In TG mice, ALM (30 mg/kg) paradoxically induced a transient increase in active wakefulness. Core body temperature (Tb) decreased after acute Hcrt receptor blockade, but the reduction in Tb that normally accompanies the wake-to-sleep transition was blunted in TG mice.
Sleep. 2013 Mar 1;36(3):325-36
Mice
Wild-type and knockout mice
Oral
25, 50, 100, 200, 300 mg/kg
Single dose
To study the effects of Almorexant on sleep and locomotor activity
Sleep. 2012 Dec 1;35(12):1625-35
Wild-type and prepro-orexin knockout mice
Wild-type and prepro-orexin knockout mice
Oral
30 and 100 mg/kg
Single dose, observed for 6 hours
To examine the effects of Almorexant on sleep-wake behavior and cataplexy. Results showed that Almorexant significantly increased NREM and REM sleep in wild-type mice but had no effect in prepro-orexin knockout mice. In the presence of chocolate, Almorexant significantly increased cataplexy episodes.
Sleep. 2020 Jun 15;43(6):zsz302
Mice
Kcna1 -null mouse model
Intraperitoneal injection
100 mg/kg
Once daily for 3 consecutive days
To evaluate the effects of Almorexant on sleep and seizures in Kcna1 -null mice. Results showed that Almorexant significantly increased the number and duration of NREM sleep epochs, reduced the latency to REM sleep onset, and decreased the incidence of severe seizures and overall seizure burden.
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