WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H300141
CAS#: 913358-93-7 (HCl)
Description: Almorexant HCl, also known as ACT-078573, is an orexin antagonist, functioning as a competitive receptor antagonist of the OX1 and OX2 orexin receptors, which was being developed by the pharmaceutical companies Actelion and GSK for the treatment of insomnia. Development of the drug was abandoned in January 2011. Almorexant is a competitive, dual OX1 and OX2 receptor antagonist and selectively inhibits the functional consequences of OX1 and OX2 receptor activation, such as intracellular Ca2+ mobilization.
Hodoodo Cat#: H300141
Name: Almorexant HCl
CAS#: 913358-93-7 (HCl)
Chemical Formula: C29H32ClF3N2O3
Exact Mass: 0.00
Molecular Weight: 549.030
Elemental Analysis: C, 63.44; H, 5.88; Cl, 6.46; F, 10.38; N, 5.10; O, 8.74
Related CAS #: 913358-93-7 (HCl) 871224-64-5 (free base),
Synonym: ACT078573; ACT 078573; ACT-078573; Almorexant; Almorexant HCl.
IUPAC/Chemical Name: (R)-2-((S)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-3,4-dihydroisoquinolin-2(1H)-yl)-N-methyl-2-phenylacetamide hydrochloride
InChi Key: BYGBTDRDPBJUBB-LHIMUUITSA-N
InChi Code: InChI=1S/C29H31F3N2O3.ClH/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);1H/t24-,27+;/m0./s1
SMILES Code: O=C([C@H](N1CCC2=C([C@@H]1CCC3=CC=C(C=C3)C(F)(F)F)C=C(C(OC)=C2)OC)C4=CC=CC=C4)NC.[H]Cl
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: >2 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:
| Biological target: | Almorexant hydrochloride (ACT 078573 hydrochloride) 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, 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; p95% 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 | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 55.3 | 100.78 | |
| DMSO:PBS (pH 7.2) (1:2) | 0.3 | 0.46 | |
| DMF | 20.0 | 36.43 | |
| Ethanol | 55.0 | 100.18 |
The following data is based on the product molecular weight 549.03 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.
| 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)
