almorexant: a dual orexin receptor antagonist for treatment of insomnia [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]
| ID Source | ID |
|---|---|
| PubMed CID | 23727689 |
| CHEMBL ID | 455136 |
| CHEBI ID | 177401 |
| SCHEMBL ID | 196577 |
| MeSH ID | M0509156 |
| Synonym |
|---|
| CHEBI:177401 |
| 871224-64-5 |
| (2r)-2-[(1s)-6,7-dimethoxy-1-[2-[4-(triluoromethyl)phenyl]ethyl]-3,4-dihydro-1h-isoquinolin-2-yl]-n-methyl-2-phenylacetamide |
| gtpl2886 |
| (2r)-2-[(1s)-6,7-dimethoxy-1-[2-[4-(trifluoromethyl)phenyl]ethyl]-3,4-dihydro-1h-isoquinolin-2-yl]-n-methyl-2-phenylacetamide |
| almorexant |
| act-078573 |
| CHEMBL455136 , |
| bdbm50292929 |
| D09964 |
| almorexant (inn) |
| 9kcw39p2ei , |
| (2r)-2-((1s)-6,7-dimethoxy-1-{2-(4-(trifluoromethyl)phenyl)ethyl}-3,4-dihydroisoquinolin-2(1h)-yl)-n-methyl-2-phenylacetamide |
| unii-9kcw39p2ei |
| almorexant [inn] |
| ((2r)-2-((1s)-6,7-dimethoxy-1-(2-(4-trifluoromethylphenyl)-ethyl)-3,4-dihydro-1h-isoquinolin-2-yl)-n-methyl-2-phenylacetamide) |
| BCP9000275 |
| AKOS016011276 |
| BCPP000414 |
| HY-10805 |
| 913358-93-7 |
| SCHEMBL196577 |
| almorexant [who-dd] |
| almorexant [mi] |
| (2r)-2-((1s)-6,7-dimethoxy-1-(2-(4-(trifluoromethyl)phenyl)ethyl)-3,4-dihydroisoquinolin-2(1h)-yl)-n-methyl-2-phenylacetamide |
| 1266467-63-3 |
| (r)-2-((s)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-3,4-dihydroisoquinolin-2(1h)-yl)-n-methyl-2-phenylacetamide |
| AC-24400 |
| (r)-2-((r)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-3,4-dihydroisoquinolin-2(1h)-yl)-n-methyl-2-phenylacetamide |
| mfcd22419385 |
| (r)-2-((s)-6,7-dimethoxy-1-(4-(trifluoromethyl)phenethyl)-3,4-dihydroisoquinolin-2(1h)-yl)-n-methyl- |
| NCGC00378603-03 |
| Q4355941 |
| DB06673 |
| (2r)-2-{(1s)-6,7-dimethoxy-1-[2-(4-trifluoromethyl-phenyl)-ethyl]-3,4-dihydro-1h-isoquinolin-2-yl}-n-methyl-2-phenyl-acetamide |
| AS-17049 |
| BCP02616 |
| DTXSID801007352 |
Almorexant is a dual orexin receptor antagonist (DORA) with sleep-enabling effects in humans. It is being developed by Actelion Ltd and GlaxoSmithKline plc for the treatment of primary insomnia.
| Excerpt | Reference | Relevance |
|---|---|---|
| "Almorexant is a dual orexin receptor antagonist (DORA) with sleep-enabling effects in humans. " | ( Pharmacokinetic and pharmacodynamic interactions between almorexant, a dual orexin receptor antagonist, and desipramine. Alessi, F; Cruz, HG; Dingemanse, J; Hay, JL; Hoever, P; te Beek, ET; van Gerven, JM, 2014) | 2.09 |
| "Almorexant (ACT-078573) is an orally active dual orexin receptor antagonist that is being developed by Actelion Ltd, in collaboration with GlaxoSmithKline plc, for the treatment of primary insomnia. " | ( Almorexant, a dual orexin receptor antagonist for the treatment of insomnia. Neubauer, DN, 2010) | 3.25 |
| "Almorexant is a selective, orally available dual orexin receptor antagonist." | ( Dual orexin receptor antagonism by almorexant does not potentiate impairing effects of alcohol in humans. de Kam, ML; Dingemanse, J; Hay, JL; Hoch, M; Hoever, P; te Beek, ET; van Gerven, JM, 2013) | 1.39 |
| Excerpt | Reference | Relevance |
|---|---|---|
| "Almorexant promotes sleep and exacerbates cataplexy in a murine model of narcolepsy." | ( Almorexant promotes sleep and exacerbates cataplexy in a murine model of narcolepsy. Black, SW; Chen, TM; Fisher, SP; Kilduff, TS; Morairty, SR; Warrier, DR, 2013) | 2.55 |
Rats treated with almorexant learned the spatial navigation task with similar efficacy as vehicle-treated animals. Rats are fully capable of spatial and avoidance learning.
| Excerpt | Reference | Relevance |
|---|---|---|
| "Rats treated with almorexant learned the spatial navigation task with similar efficacy as vehicle-treated animals. " | ( Intact learning and memory in rats following treatment with the dual orexin receptor antagonist almorexant. Dietrich, H; Jenck, F, 2010) | 0.91 |
| "Rats treated with almorexant are fully capable of spatial and avoidance learning." | ( Intact learning and memory in rats following treatment with the dual orexin receptor antagonist almorexant. Dietrich, H; Jenck, F, 2010) | 0.91 |
| Excerpt | Reference | Relevance |
|---|---|---|
| " Adverse events were similar with almorexant and placebo." | ( Efficacy and safety of almorexant in adult chronic insomnia: a randomized placebo-controlled trial with an active reference. Berkani, O; Black, J; Hajak, G; Hedner, J; Hmissi, A; Mangialaio, S; Pillar, G; Polo, O; Zammit, G, 2017) | 1.04 |
The pharmacokinetic parameters of almorexant were calculated by noncompartmental analysis from the plasma concentration data. A single-center, randomized, placebo-controlled, two-way crossover study in 20 healthy male subjects was conducted.
| Excerpt | Reference | Relevance |
|---|---|---|
| " The pharmacokinetic parameters of almorexant were calculated by noncompartmental analysis from the plasma concentration data." | ( Pharmacokinetics and tolerability of almorexant in Japanese and Caucasian healthy male subjects. Alessi, F; Dingemanse, J; Hoch, M; Hoever, P; Marjason, J, 2011) | 0.92 |
| "4) in the maximum plasma concentration (C(max)), area under the concentration-time curve from time 0 to infinity (AUC(0-∞)), and terminal half-life (t(1/2)), respectively, of midazolam; the time to peak plasma concentration (t(max)) was unchanged." | ( Pharmacokinetic interactions of almorexant with midazolam and simvastatin, two CYP3A4 model substrates, in healthy male subjects. Alessi, F; Dingemanse, J; Hoch, M; Hoever, P; Theodor, R, 2013) | 0.67 |
| " The main pharmacodynamic variable was the AUC for the international normalized ratio (AUCINR)." | ( Absence of pharmacokinetic and pharmacodynamic interactions between almorexant and warfarin in healthy subjects. Dingemanse, J; Hoever, P, 2013) | 0.63 |
| " Two randomized two-way crossover studies were performed in healthy subjects investigating the pharmacokinetic interaction between almorexant and the CYP3A4 inhibitors ketoconazole and diltiazem." | ( Pharmacokinetic interactions between the orexin receptor antagonist almorexant and the CYP3A4 inhibitors ketoconazole and diltiazem. Cruz, HG; Dingemanse, J; Gehin, M; Hoever, P, 2014) | 0.84 |
| " A single-center, randomized, placebo-controlled, two-way crossover study in 20 healthy male subjects was conducted to evaluate the pharmacokinetic and pharmacodynamic interactions between almorexant and desipramine." | ( Pharmacokinetic and pharmacodynamic interactions between almorexant, a dual orexin receptor antagonist, and desipramine. Alessi, F; Cruz, HG; Dingemanse, J; Hay, JL; Hoever, P; te Beek, ET; van Gerven, JM, 2014) | 0.84 |
| Excerpt | Reference | Relevance |
|---|---|---|
| "Current insomnia treatments such as γ-aminobutyric acid (GABA) receptor modulators are associated with sedative and muscle-relaxant effects, which increase when drug intake is combined with alcohol." | ( Differential effects of the dual orexin receptor antagonist almorexant and the GABA(A)-α1 receptor modulator zolpidem, alone or combined with ethanol, on motor performance in the rat. Brisbare-Roch, C; Jenck, F; Lecourt, H; Steiner, MA; Strasser, DS, 2011) | 0.61 |
The absolute oral bioavailability of almorexant was 11. The active pharmaceutical ingredient (API) was sticking to the apparatus used during tablet compression.
| Excerpt | Relevance | Reference |
|---|---|---|
| "Intracerebroventricular orexin A; oral dosing of almorexant." | ( The dual orexin receptor antagonist almorexant induces sleep and decreases orexin-induced locomotion by blocking orexin 2 receptors. Abramowski, D; Bürki, H; Dürst, T; Fendt, M; Gee, CE; Hoyer, D; Imobersteg, S; Mang, GM; Schuepbach, E, 2012) | 0.91 |
| " Chronic dosing was not associated with a change in effect size or sleep architecture immediately postdosing." | ( Preclinical in vivo characterization of lemborexant (E2006), a novel dual orexin receptor antagonist for sleep/wake regulation. Akasofu, S; Beuckmann, CT; Nakagawa, M; Suzuki, M; Ueno, T, 2019) | 0.51 |
| Class | Description |
|---|---|
| isoquinolines | A class of organic heteropolycyclic compound consisting of isoquinoline and its substitution derivatives. |
| [compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res] | |
| Protein | Taxonomy | Measurement | Average (µ) | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| cytochrome P450 family 3 subfamily A polypeptide 4 | Homo sapiens (human) | Potency | 2.1317 | 0.0123 | 7.9835 | 43.2770 | AID1645841 |
| G | Vesicular stomatitis virus | Potency | 6.7412 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| cytochrome P450 2D6 | Homo sapiens (human) | Potency | 4.7724 | 0.0010 | 8.3798 | 61.1304 | AID1645840 |
| Interferon beta | Homo sapiens (human) | Potency | 6.7412 | 0.0033 | 9.1582 | 39.8107 | AID1645842 |
| HLA class I histocompatibility antigen, B alpha chain | Homo sapiens (human) | Potency | 6.7412 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| Inositol hexakisphosphate kinase 1 | Homo sapiens (human) | Potency | 6.7412 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| cytochrome P450 2C9, partial | Homo sapiens (human) | Potency | 6.7412 | 0.0123 | 8.9648 | 39.8107 | AID1645842 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Protein | Taxonomy | Measurement | Average | Min (ref.) | Avg (ref.) | Max (ref.) | Bioassay(s) |
|---|---|---|---|---|---|---|---|
| Orexin receptor type 1 | Homo sapiens (human) | IC50 (µMol) | 0.0395 | 0.0060 | 0.0445 | 0.1990 | AID1279975; AID347760; AID755917; AID767538 |
| Orexin receptor type 1 | Homo sapiens (human) | Ki | 0.0130 | 0.0003 | 0.2876 | 3.1623 | AID765089 |
| Orexin receptor type 2 | Homo sapiens (human) | IC50 (µMol) | 2.0310 | 0.0004 | 0.5185 | 8.1000 | AID1279976; AID347761; AID755916; AID767536 |
| Orexin receptor type 2 | Homo sapiens (human) | Ki | 0.0064 | 0.0002 | 0.3771 | 3.7810 | AID1166953; AID765090 |
| Sigma non-opioid intracellular receptor 1 | Rattus norvegicus (Norway rat) | Ki | 0.0080 | 0.0003 | 0.2671 | 5.0700 | AID765090 |
| [prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023] | |||||||
| Assay ID | Title | Year | Journal | Article |
|---|---|---|---|---|
| AID1346986 | P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen | 2019 | Molecular pharmacology, 11, Volume: 96, Issue:5 | A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. |
| AID1347160 | Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors | 2020 | Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49 | Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. |
| AID1296008 | Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening | 2020 | SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1 | Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening. |
| AID1347159 | Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay | 2020 | Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49 | Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors. |
| AID1346987 | P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen | 2019 | Molecular pharmacology, 11, Volume: 96, Issue:5 | A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. |
| AID1280035 | Effect on sleep parameter in insomnia patient assessed as total sleep time at 100 mg, po by polysomnography | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1279968 | Half life in iv dosed Wistar rat | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1279980 | Effect on sleep parameter in Wistar rat assessed as latency to persistent REM time at 100 mg/kg, po measured over 12 hrs (Rvb = 101 +/- 17 min) | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID767536 | Antagonist activity at OX2 receptor (unknown origin) | 2013 | Journal of medicinal chemistry, Sep-12, Volume: 56, Issue:17 | Substituted tetrahydroisoquinolines as selective antagonists for the orexin 1 receptor. |
| AID1219610 | Absolute bioavailability in po dosed healthy human | 2013 | Drug metabolism and disposition: the biological fate of chemicals, May, Volume: 41, Issue:5 | Elucidation of the metabolic pathways and the resulting multiple metabolites of almorexant, a dual orexin receptor antagonist, in humans. |
| AID1219608 | Volume of distribution in po dosed healthy human | 2013 | Drug metabolism and disposition: the biological fate of chemicals, May, Volume: 41, Issue:5 | Elucidation of the metabolic pathways and the resulting multiple metabolites of almorexant, a dual orexin receptor antagonist, in humans. |
| AID1198883 | Induction of sleep in Wistar rat assessed as time spent in quiet wake at 100 mg/kg, po after 12 hrs (Rvb = 32.8%) | 2015 | Bioorganic & medicinal chemistry letters, May-01, Volume: 25, Issue:9 | Substituted pyrrolidin-2-ones: Centrally acting orexin receptor antagonists promoting sleep. Part 2. |
| AID1280033 | Effect on sleep parameter in insomnia patient assessed as latency to persistent sleep time at 100 mg, po by polysomnography | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1280040 | Effect on sleep parameter in insomnia patient assessed as sleep efficiency at 400 mg, po by polysomnography | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1280037 | Effect on sleep parameter in insomnia patient assessed as latency to persistent sleep time at 200 mg, po by polysomnography | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID755907 | Sleep-promoting activity in Wistar rat electroencephalographic model assessed as increase in time spent in non-rapid eye movement sleep at 100 mg/kg, po measured over 12 hrs relative to vehicle-treated control | 2013 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 23, Issue:13 | Structure-activity relationship studies and sleep-promoting activity of novel 1-chloro-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine derivatives as dual orexin receptor antagonists. Part 2. |
| AID1166953 | Displacement of [125I]-Orexin A from human OX2R expressed in CHO cells after 30 mins by topcount analysis | 2014 | Bioorganic & medicinal chemistry, Nov-01, Volume: 22, Issue:21 | Design, synthesis, and structure-activity relationships of a series of novel N-aryl-2-phenylcyclopropanecarboxamide that are potent and orally active orexin receptor antagonists. |
| AID1279965 | Effect on sleep parameter in po dosed Beagle dog by EEG analysis | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1280042 | Effect on sleep parameter in insomnia patient assessed as wake after sleep onset time at 400 mg, po by polysomnography | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID347760 | Inhibition of OX1 receptor | 2009 | Journal of medicinal chemistry, Feb-26, Volume: 52, Issue:4 | Biomedical application of orexin/hypocretin receptor ligands in neuroscience. |
| AID1279975 | Antagonist activity at human OX1R expressed in CHO cells assessed as inhibition of orexin-A-induced intracellular calcium release | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1219606 | Terminal half life in po dosed healthy human | 2013 | Drug metabolism and disposition: the biological fate of chemicals, May, Volume: 41, Issue:5 | Elucidation of the metabolic pathways and the resulting multiple metabolites of almorexant, a dual orexin receptor antagonist, in humans. |
| AID1280039 | Effect on sleep parameter in insomnia patient assessed as total sleep time at 200 mg, po by polysomnography | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1280027 | Tmax in human at 1 to 1000 mg administered as single dose | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1279971 | Effect on sleep parameter in po dosed Wistar rat by EEG analysis | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1279961 | Plasma protein binding in Wistar rat | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1280031 | Effect on sleep parameter in insomnia patient assessed as total sleep time at 50 mg, po by polysomnography | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1280036 | Effect on sleep parameter in insomnia patient assessed as sleep efficiency at 200 mg, po by polysomnography | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1279976 | Antagonist activity at human OX2R expressed in CHO cells assessed as inhibition of orexin-A-induced intracellular calcium release | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1219609 | Tmax in po dosed healthy human receiving additional evening dose | 2013 | Drug metabolism and disposition: the biological fate of chemicals, May, Volume: 41, Issue:5 | Elucidation of the metabolic pathways and the resulting multiple metabolites of almorexant, a dual orexin receptor antagonist, in humans. |
| AID1279970 | Oral bioavailability in Beagle dog | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1280032 | Effect on sleep parameter in insomnia patient assessed as sleep efficiency at 100 mg, po by polysomnography | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1280028 | Effect on sleep parameter in insomnia patient assessed as sleep efficiency at 50 mg, po by polysomnography | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID765089 | Binding affinity to orexin receptor 1 (unknown origin) | 2013 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 23, Issue:17 | Selective orexin receptor antagonists. |
| AID1198885 | Induction of sleep in Wistar rat assessed as time spent in REM sleep at 100 mg/kg, po after 12 hrs (Rvb = 4.7%) | 2015 | Bioorganic & medicinal chemistry letters, May-01, Volume: 25, Issue:9 | Substituted pyrrolidin-2-ones: Centrally acting orexin receptor antagonists promoting sleep. Part 2. |
| AID1279967 | Ratio of drug level in brain to plasma in Wistar rat | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1279978 | Effect on sleep parameter in Wistar rat assessed as REM sleep duration time at 100 mg/kg, po measured over 12 hrs (Rvb = 33 +/- 4 min) | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID755904 | Sleep-promoting activity in Wistar rat electroencephalographic model assessed as increase in time spent in rapid eye movement sleep at 100 mg/kg, po measured over 12 hrs relative to vehicle-treated control | 2013 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 23, Issue:13 | Structure-activity relationship studies and sleep-promoting activity of novel 1-chloro-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine derivatives as dual orexin receptor antagonists. Part 2. |
| AID755905 | Sleep-promoting activity in Wistar rat electroencephalographic model assessed as time spent in non-rapid eye movement sleep at 100 mg/kg, po measured over 12 hrs relative to total sleep time (Rvb = 85.4 to 87.3%) | 2013 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 23, Issue:13 | Structure-activity relationship studies and sleep-promoting activity of novel 1-chloro-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine derivatives as dual orexin receptor antagonists. Part 2. |
| AID1279977 | Effect on sleep parameter in Wistar rat assessed as NREM sleep duration time at 100 mg/kg, po measured over 12 hrs (Rvb = 243 +/- 8 min) | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1219607 | Clearance in po dosed healthy human | 2013 | Drug metabolism and disposition: the biological fate of chemicals, May, Volume: 41, Issue:5 | Elucidation of the metabolic pathways and the resulting multiple metabolites of almorexant, a dual orexin receptor antagonist, in humans. |
| AID1198882 | Induction of sleep in Wistar rat assessed as time spent in active wake at 100 mg/kg, po after 12 hrs (Rvb = 30%) | 2015 | Bioorganic & medicinal chemistry letters, May-01, Volume: 25, Issue:9 | Substituted pyrrolidin-2-ones: Centrally acting orexin receptor antagonists promoting sleep. Part 2. |
| AID767538 | Antagonist activity at OX1 receptor (unknown origin) | 2013 | Journal of medicinal chemistry, Sep-12, Volume: 56, Issue:17 | Substituted tetrahydroisoquinolines as selective antagonists for the orexin 1 receptor. |
| AID1198884 | Induction of sleep in Wistar rat assessed as time spent in non-REM sleep at 100 mg/kg, po after 12 hrs (Rvb = 32.1%) | 2015 | Bioorganic & medicinal chemistry letters, May-01, Volume: 25, Issue:9 | Substituted pyrrolidin-2-ones: Centrally acting orexin receptor antagonists promoting sleep. Part 2. |
| AID755909 | Sleep-promoting activity in Wistar rat electroencephalographic model assessed as decrease in home cage activity at 100 mg/kg, po measured over 12 hrs relative to vehicle-treated control | 2013 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 23, Issue:13 | Structure-activity relationship studies and sleep-promoting activity of novel 1-chloro-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine derivatives as dual orexin receptor antagonists. Part 2. |
| AID1280030 | Effect on sleep parameter in insomnia patient assessed as wake after sleep onset time at 50 mg, po by polysomnography | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1280038 | Effect on sleep parameter in insomnia patient assessed as wake after sleep onset time at 200 mg, po by polysomnography | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1198876 | Induction of sleep in Wistar rat assessed as decrease in home cage activity at 100 mg/kg, po after 12 hrs relative to control | 2015 | Bioorganic & medicinal chemistry letters, May-01, Volume: 25, Issue:9 | Substituted pyrrolidin-2-ones: Centrally acting orexin receptor antagonists promoting sleep. Part 2. |
| AID755906 | Sleep-promoting activity in Wistar rat electroencephalographic model assessed as time spent in rapid eye movement sleep at 100 mg/kg, po measured over 12 hrs relative to total sleep time (Rvb = 12.7 to 14.6%) | 2013 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 23, Issue:13 | Structure-activity relationship studies and sleep-promoting activity of novel 1-chloro-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine derivatives as dual orexin receptor antagonists. Part 2. |
| AID755917 | Antagonist activity at human OX1R expressed in CHO cells assessed as inhibition of calcium mobilization by FLIPR assay | 2013 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 23, Issue:13 | Structure-activity relationship studies and sleep-promoting activity of novel 1-chloro-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine derivatives as dual orexin receptor antagonists. Part 2. |
| AID1279981 | Oral bioavailability in human | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID755908 | Sleep-promoting activity in Wistar rat electroencephalographic model assessed as reduction of time spent in active wake at 100 mg/kg, po measured over 12 hrs relative to vehicle-treated control | 2013 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 23, Issue:13 | Structure-activity relationship studies and sleep-promoting activity of novel 1-chloro-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine derivatives as dual orexin receptor antagonists. Part 2. |
| AID765090 | Binding affinity to orexin receptor 2 (unknown origin) | 2013 | Bioorganic & medicinal chemistry letters, Sep-01, Volume: 23, Issue:17 | Selective orexin receptor antagonists. |
| AID1280041 | Effect on sleep parameter in insomnia patient assessed as latency to persistent sleep time at 400 mg, po by polysomnography | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID347761 | Inhibition of OX2 receptor | 2009 | Journal of medicinal chemistry, Feb-26, Volume: 52, Issue:4 | Biomedical application of orexin/hypocretin receptor ligands in neuroscience. |
| AID1279969 | Oral bioavailability in Wistar rat | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1280029 | Effect on sleep parameter in insomnia patient assessed as latency to persistent sleep time at 50 mg, po by polysomnography | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1219605 | Tmax in po dosed healthy human | 2013 | Drug metabolism and disposition: the biological fate of chemicals, May, Volume: 41, Issue:5 | Elucidation of the metabolic pathways and the resulting multiple metabolites of almorexant, a dual orexin receptor antagonist, in humans. |
| AID1280034 | Effect on sleep parameter in insomnia patient assessed as wake after sleep onset time at 100 mg, po by polysomnography | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1279979 | Effect on sleep parameter in Wistar rat assessed as latency to persistent NREM time at 100 mg/kg, po measured over 12 hrs (Rvb = 40 +/- 3 min) | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1279962 | Elimination half life in human at 1 to 1000 mg administered as single dose | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID755916 | Antagonist activity at human OX2R expressed in CHO cells assessed as inhibition of calcium mobilization by FLIPR assay | 2013 | Bioorganic & medicinal chemistry letters, Jul-01, Volume: 23, Issue:13 | Structure-activity relationship studies and sleep-promoting activity of novel 1-chloro-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine derivatives as dual orexin receptor antagonists. Part 2. |
| AID1279966 | Ratio of drug level in CSF to plasma in Wistar rat | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1280043 | Effect on sleep parameter in insomnia patient assessed as total sleep time at 400 mg, po by polysomnography | 2016 | Journal of medicinal chemistry, Jan-28, Volume: 59, Issue:2 | Orexin Receptor Antagonists: New Therapeutic Agents for the Treatment of Insomnia. |
| AID1346418 | Human OX2 receptor (Orexin receptors) | 2007 | Nature medicine, Feb, Volume: 13, Issue:2 | Promotion of sleep by targeting the orexin system in rats, dogs and humans. |
| AID1346381 | Human OX1 receptor (Orexin receptors) | 2007 | Nature medicine, Feb, Volume: 13, Issue:2 | Promotion of sleep by targeting the orexin system in rats, dogs and humans. |
| [information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||||
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 10 (12.20) | 29.6817 |
| 2010's | 65 (79.27) | 24.3611 |
| 2020's | 7 (8.54) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.
| This Compound (30.00) All Compounds (24.57) |
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 21 (25.00%) | 5.53% |
| Reviews | 8 (9.52%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 55 (65.48%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||