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Chemical Structure| 913358-93-7 Chemical Structure| 913358-93-7

Structure of Almorexant HCl
CAS No.: 913358-93-7

Chemical Structure| 913358-93-7

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Almorexant HCl 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.

Synonyms: ACT 078573 hydrochloride; Almorexant (hydrochloride); ACT 078573

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Product Details of Almorexant HCl

CAS No. :913358-93-7
Formula : C29H35ClN2O3
M.W : 495.05
SMILES Code : O=C(NC)[C@H](N1[C@@H](CCC2=CC=C(C(F)(F)F)C=C2)C3=C(C=C(OC)C(OC)=C3)CC1)C4=CC=CC=C4.[H]Cl
Synonyms :
ACT 078573 hydrochloride; Almorexant (hydrochloride); ACT 078573
MDL No. :MFCD14636620

Safety of Almorexant HCl

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

Target
  • OX1 receptor

    OX1 receptor, IC50:6.6 nM

  • OX2 receptor

    OX2 receptor, IC50:3.4 nM

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice Grm2-Cre mice Intraperitoneal injection 30 mg/kg Single dose Almorexant largely reversed the sleep fragmentation observed in LHb-TeLC mice, reducing wake time and increasing NREM sleep time, but had no significant effect on REM sleep time. PMC5835141
Wistar rats Accelerating rotating rod (rotarod) and forepaw grip strength tests Oral 30, 100, and 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. Results showed that Almorexant did not affect motor performance and did not further increase the sedative effects of ethanol when combined. PMC3055732
Mice Wild-type and knockout mice Oral 25, 50, 100, 200, 300 mg/kg Single dose Investigate the effects of Almorexant on sleep and locomotor activity PMC3490355
BALB/c mice Unpredictable chronic mild stress (UCMS) model Oral 100 mg/kg Daily administration for 7 weeks To investigate the antidepressant-like effects of almorexant on UCMS-induced behavioral and physiological alterations. 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 but did not increase hippocampal cell proliferation and neurogenesis. PMC3422486
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. Results showed that 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. PMC3571748
Rats Post-traumatic stress disorder (PTSD) animal model Intraperitoneal injection 150 mg/kg Single dose, observed for 7 days Evaluate the effect of Almorexant on behavioral responses after PSS exposure, results showed that Almorexant increased the prevalence of PTSD phenotype. PMC7026175
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 activation of Hcrt, HA, and ACh neurons during forced wakefulness, whereas ZOL inhibits activation of these cell groups. PMC4748439
Mice Wild-type mice and prepro-orexin knockout mice Oral 30 and 100 mg/kg Single administration, observed for 6 hours To study the effects of Almorexant on sleep-wake behavior and cataplexy. Results showed that Almorexant dose-dependently increased NREM and REM sleep and increased cataplexy when combined with chocolate. PMC7294412
Mice Kcna1 -null mice 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. PMC4712395
Rats Upper airway obstruction model Oral gavage 300 mg/kg Once daily for 8 days To investigate the effect of Almorexant on sleep and growth plate morphology. Results showed that Almorexant significantly improved sleep and growth plate width in AO animals. PMC4791622

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.02mL

0.40mL

0.20mL

10.10mL

2.02mL

1.01mL

20.20mL

4.04mL

2.02mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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