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MedKoo Cat#: 573682 | Name: Almorexant
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Almorexant, also known as ACT-078573, is a competitive receptor antagonist of the OX1 and OX2 orexin receptors. Almorexant selectively inhibits the functional consequences of OX1 and OX2 receptor activation, such as intracellular Ca2+ mobilization.

Chemical Structure

Almorexant
CAS#871224-64-5 (free base)

Theoretical Analysis

MedKoo Cat#: 573682

Name: Almorexant

CAS#: 871224-64-5 (free base)

Chemical Formula: C29H31F3N2O3

Exact Mass: 512.2287

Molecular Weight: 512.57

Elemental Analysis: C, 67.95; H, 6.10; F, 11.12; N, 5.47; O, 9.36

Price and Availability

Size Price Availability Quantity
5mg USD 350.00 2 Weeks
10mg USD 650.00 2 Weeks
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Related CAS #
913358-93-7 (HCl) 871224-64-5 (free base)
Synonym
ACT-078573, Almorexant
IUPAC/Chemical Name
(2R)-2-((1S)-6,7-dimethoxy-1-{2-(4-(trifluoromethyl)phenyl)ethyl}-3,4-dihydroisoquinolin-2(1H)-yl)-N-methyl-2-phenylacetamide
InChi Key
DKMACHNQISHMDN-RPLLCQBOSA-N
InChi Code
1S/C29H31F3N2O3/c1-33-28(35)27(20-7-5-4-6-8-20)34-16-15-21-17-25(36-2)26(37-3)18-23(21)24(34)14-11-19-9-12-22(13-10-19)29(30,31)32/h4-10,12-13,17-18,24,27H,11,14-16H2,1-3H3,(H,33,35)/t24-,27+/m0/s1
SMILES Code
CNC(=O)[C@H](N1CCc2cc(OC)c(OC)cc2[C@@H]1CCc3ccc(cc3)C(F)(F)F)c4ccccc4
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
Almorexant (ACT 078573) is a dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist with Ki values of 1.3 and 0.17 nM, respectively.
In vitro activity:
TBD
In vivo activity:
The doses of ALM (Almorexant) and ZOL used in the present study (100 mg/kg, p.o) were chosen because they have roughly equivalent sleep induction efficacy in rats and, for ALM, result in high occupancy of both Hcrt receptors. Both ALM and ZOL significantly decreased the latency to first NREM sleep bout relative to VEH (18.6±2.6 min for ALM, 16.1±3.9 min for ZOL vs 36.7±7.6 min for VEH; p<0.05 for both comparisons with VEH) in rats left undisturbed after dosing. Significant interactions between time and drug treatment were found in undisturbed animals for wake (F(6,42)=4.34; p=0.002) and NREM (F(6,42)=3.86; p=0.004) time during the 90 min period post dosing. Both ALM- and ZOL-treated rats exhibited less time awake and more time in NREM than VEH-treated rats; no differences were found between ALM- and ZOL-treated rats (Figure 1b and c). For REM sleep, a main effect was found for drug treatment (F(2,14)=6.074; p=0.01) that was largely due to ALM treatment (Figure 1d). SD was highly effective for all groups, as rats were awake >95% of the time during SD regardless of drug treatment (Figure 1e). Reference: Neuropsychopharmacology. 2016 Mar; 41(4): 1144–1155. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748439/
Solvent mg/mL mM comments
Solubility
DMSO 46.0 89.74
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 512.57 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Parks GS, Warrier DR, Dittrich L, Schwartz MD, Palmerston JB, Neylan TC, Morairty SR, Kilduff TS. The Dual Hypocretin Receptor Antagonist Almorexant is Permissive for Activation of Wake-Promoting Systems. Neuropsychopharmacology. 2016 Mar;41(4):1144-55. doi: 10.1038/npp.2015.256. Epub 2015 Aug 20. PMID: 26289145; PMCID: PMC4748439. 2. Morairty SR, Wilk AJ, Lincoln WU, Neylan TC, Kilduff TS. The hypocretin/orexin antagonist almorexant promotes sleep without impairment of performance in rats. Front Neurosci. 2014 Jan 31;8:3. doi: 10.3389/fnins.2014.00003. PMID: 24550767; PMCID: PMC3907703.
In vitro protocol:
TBD
In vivo protocol:
1. Parks GS, Warrier DR, Dittrich L, Schwartz MD, Palmerston JB, Neylan TC, Morairty SR, Kilduff TS. The Dual Hypocretin Receptor Antagonist Almorexant is Permissive for Activation of Wake-Promoting Systems. Neuropsychopharmacology. 2016 Mar;41(4):1144-55. doi: 10.1038/npp.2015.256. Epub 2015 Aug 20. PMID: 26289145; PMCID: PMC4748439. 2. Morairty SR, Wilk AJ, Lincoln WU, Neylan TC, Kilduff TS. The hypocretin/orexin antagonist almorexant promotes sleep without impairment of performance in rats. Front Neurosci. 2014 Jan 31;8:3. doi: 10.3389/fnins.2014.00003. PMID: 24550767; PMCID: PMC3907703.
1: Abad VC, Guilleminault C. Insomnia in Elderly Patients: Recommendations for Pharmacological Management. Drugs Aging. 2018 Sep;35(9):791-817. doi: 10.1007/s40266-018-0569-8. PMID: 30058034. 2: Neubauer DN. Almorexant, a dual orexin receptor antagonist for the treatment of insomnia. Curr Opin Investig Drugs. 2010 Jan;11(1):101-10. PMID: 20047164. 3: Wu X, Xue T, Chen Z, Wang Z, Chen G. Orexin Receptor Antagonists and Insomnia. Curr Psychiatry Rep. 2022 Oct;24(10):509-521. doi: 10.1007/s11920-022-01357-w. Epub 2022 Aug 16. PMID: 35972717. 4: Hoch M, Hoever P, Theodor R, Dingemanse J. Almorexant effects on CYP3A4 activity studied by its simultaneous and time-separated administration with simvastatin and atorvastatin. Eur J Clin Pharmacol. 2013 Jun;69(6):1235-45. doi: 10.1007/s00228-012-1470-8. Epub 2013 Jan 20. PMID: 23334403. 5: Berro LF, Moreira-Junior EDC, Rowlett JK. The dual orexin receptor antagonist almorexant blocks the sleep-disrupting and daytime stimulant effects of methamphetamine in rhesus monkeys. Drug Alcohol Depend. 2021 Oct 1;227:108930. doi: 10.1016/j.drugalcdep.2021.108930. Epub 2021 Jul 28. PMID: 34358767; PMCID: PMC8464508. 6: Cruz HG, Hay JL, Hoever P, Alessi F, te Beek ET, van Gerven JM, Dingemanse J. Pharmacokinetic and pharmacodynamic interactions between almorexant, a dual orexin receptor antagonist, and desipramine. Eur Neuropsychopharmacol. 2014 Aug;24(8):1257-68. doi: 10.1016/j.euroneuro.2014.05.002. Epub 2014 May 13. PMID: 24880753. 7: Hoch M, Hoever P, Alessi F, Marjason J, Dingemanse J. Pharmacokinetics and tolerability of almorexant in Japanese and Caucasian healthy male subjects. Pharmacology. 2011;88(3-4):121-6. doi: 10.1159/000330098. Epub 2011 Aug 25. PMID: 21865769. 8: Imperatore R, Palomba L, Cristino L. Role of Orexin-A in Hypertension and Obesity. Curr Hypertens Rep. 2017 Apr;19(4):34. doi: 10.1007/s11906-017-0729-y. PMID: 28353077. 9: Black J, Pillar G, Hedner J, Polo O, Berkani O, Mangialaio S, Hmissi A, Zammit G, Hajak G. Efficacy and safety of almorexant in adult chronic insomnia: a randomized placebo-controlled trial with an active reference. Sleep Med. 2017 Aug;36:86-94. doi: 10.1016/j.sleep.2017.05.009. Epub 2017 May 29. PMID: 28735928. 10: Hoch M, Hay JL, Hoever P, de Kam ML, te Beek ET, van Gerven JM, Dingemanse J. Dual orexin receptor antagonism by almorexant does not potentiate impairing effects of alcohol in humans. Eur Neuropsychopharmacol. 2013 Feb;23(2):107-17. doi: 10.1016/j.euroneuro.2012.04.012. Epub 2012 May 30. PMID: 22658401. 11: Roth T, Black J, Cluydts R, Charef P, Cavallaro M, Kramer F, Zammit G, Walsh J. Dual Orexin Receptor Antagonist, Almorexant, in Elderly Patients With Primary Insomnia: A Randomized, Controlled Study. Sleep. 2017 Feb 1;40(2). doi: 10.1093/sleep/zsw034. PMID: 28364509. 12: Mang GM, Dürst T, Bürki H, Imobersteg S, Abramowski D, Schuepbach E, Hoyer D, Fendt M, Gee CE. The dual orexin receptor antagonist almorexant induces sleep and decreases orexin-induced locomotion by blocking orexin 2 receptors. Sleep. 2012 Dec 1;35(12):1625-35. doi: 10.5665/sleep.2232. PMID: 23204605; PMCID: PMC3490355. 13: Hoch M, Hoever P, Zisowsky J, Priestley A, Fleet D, Dingemanse J. Absolute oral bioavailability of almorexant, a dual orexin receptor antagonist, in healthy human subjects. Pharmacology. 2012;89(1-2):53-7. doi: 10.1159/000335367. Epub 2012 Feb 1. PMID: 22302127. 14: Hoch M, Hoever P, Alessi F, Theodor R, Dingemanse J. Pharmacokinetic interactions of almorexant with midazolam and simvastatin, two CYP3A4 model substrates, in healthy male subjects. Eur J Clin Pharmacol. 2013 Mar;69(3):523-32. doi: 10.1007/s00228-012-1403-6. Epub 2012 Sep 19. PMID: 22990330. 15: Steiner MA, Lecourt H, Jenck F. The brain orexin system and almorexant in fear-conditioned startle reactions in the rat. Psychopharmacology (Berl). 2012 Oct;223(4):465-75. doi: 10.1007/s00213-012-2736-7. Epub 2012 May 17. PMID: 22592903. 16: Dingemanse J, Hoever P. Absence of pharmacokinetic and pharmacodynamic interactions between almorexant and warfarin in healthy subjects. Drugs R D. 2013 Jun;13(2):145-51. doi: 10.1007/s40268-013-0017-5. PMID: 23737453; PMCID: PMC3689907. 17: Dingemanse J, Cruz HG, Gehin M, Hoever P. Pharmacokinetic interactions between the orexin receptor antagonist almorexant and the CYP3A4 inhibitors ketoconazole and diltiazem. J Pharm Sci. 2014 May;103(5):1548-56. doi: 10.1002/jps.23916. Epub 2014 Mar 6. PMID: 24604243. 18: Dingemanse J, Gehin M, Cruz HG, Hoever P. Formulation development for the orexin receptor antagonist almorexant: assessment in two clinical studies. Drug Des Devel Ther. 2014 Apr 28;8:397-403. doi: 10.2147/DDDT.S62118. PMID: 24812492; PMCID: PMC4010641. 19: Srinivasan S, Simms JA, Nielsen CK, Lieske SP, Bito-Onon JJ, Yi H, Hopf FW, Bonci A, Bartlett SE. The dual orexin/hypocretin receptor antagonist, almorexant, in the ventral tegmental area attenuates ethanol self- administration. PLoS One. 2012;7(9):e44726. doi: 10.1371/journal.pone.0044726. Epub 2012 Sep 21. PMID: 23028593; PMCID: PMC3448615. 20: Hoever P, Hay J, Rad M, Cavallaro M, van Gerven JM, Dingemanse J. Tolerability, pharmacokinetics, and pharmacodynamics of single-dose almorexant, an orexin receptor antagonist, in healthy elderly subjects. J Clin Psychopharmacol. 2013 Jun;33(3):363-70. doi: 10.1097/JCP.0b013e31828f5a7a. PMID: 23609389.
1. Lais F. Berro, Eliseu da Cruz Moreira-Junior, James K. Rowlett, The dual orexin receptor antagonist almorexant blocks the sleep-disrupting and daytime stimulant effects of methamphetamine in rhesus monkeys, Drug and Alcohol Dependence, 2021, 108930, ISSN 0376-8716, https://doi.org/10.1016/j.drugalcdep.2021.108930. (https://www.sciencedirect.com/science/article/pii/S0376871621004257)

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