Structure of Almorexant HCl
CAS No.: 913358-93-7
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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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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 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Target |
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In Vivo:
Species
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Animal Model
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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 |
Tags: Almorexant | ACT 078573 | ACT078573 | ACT-078573 | Orexin Receptor (OX Receptor) | Calcium Channel | Caspase | Apoptosis | Hypocretin Receptor | HCRT Receptor | Ca2+ channels | Ca channels | GPCR | orexin | orexin receptor antagonist | OX1 antagonist | OX2 antagonist | apoptosis | caspase-3 | 913358-93-7
Precautionary Statements-General | |
Code | Phrase |
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P222 | Do not allow contact with air. |
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P230 | Keep wetted |
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P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
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P285 | In case of inadequate ventilation wear respiratory protection. |
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P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
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P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
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P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
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P313 | Get medical advice/attention. |
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P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
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P350 | Gently wash with plenty of soap and water. |
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P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
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P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
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P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
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P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
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Code | Phrase |
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H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
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H221 | Flammable gas |
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H224 | Extremely flammable liquid and vapour |
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H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
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H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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