Identification
- Summary
Suvorexant is a orexin receptor antagonist used to treat insomnia that is characterized by difficulties with sleep onset and/or sleep maintenance.
- Brand Names
- Belsomra
- Generic Name
- Suvorexant
- DrugBank Accession Number
- DB09034
- Background
Suvorexant is a selective dual antagonist of orexin receptors OX1R and OX2R that promotes sleep by reducing wakefulness and arousal. It has been approved for the treatment of insomnia.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Suvorexant (DB09034)
- Weight
- Average: 450.93
Monoisotopic: 450.1571017 - Chemical Formula
- C23H23ClN6O2
- Synonyms
- Suvorexant
- External IDs
- MK 4305
- MK-4305
- MK4305
Pharmacology
- Indication
Suvorexant is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.
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- Contraindications & Blackbox Warnings
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Not Available
- Mechanism of action
Suvorexant is a dual antagonist of orexin receptors OX1R and OX2R. It exerts its pharmacological effect by inhibiting binding of neuropeptides orexin A and B, also known as hypocretin 1 and 2, that are produced by neurons in the lateral hypothalamus. These neurons control the wake-promoting centers of the brain and are active during wakefulness, especially during motor activities, and stop firing during sleep. By inhibiting the reinforcement of arousal systems, suvorexant use causes a decrease in arousal and wakefulness, rather than having a direct sleep-promoting effect.
Target Actions Organism AOrexin receptor type 1 antagonistHumans AOrexin receptor type 2 antagonistHumans - Absorption
Peak concentrations occur at a median Tmax of 2 hours under fasted conditions. Ingestion of suvorexant with a high-fat meal has no effect on AUC or Cmax, but may delay Tmax by approximately 1.5 hours. Mean absolute bioavailability of 10 mg is 82%.
- Volume of distribution
Mean volume of distribution is approximately 49 litres.
- Protein binding
Suvorexant is extensively bound (>99%) to human plasma proteins and does not preferentially distribute into red blood cells. It binds to both human serum albumin and alpha1-acid glycoprotein.
- Metabolism
Suvorexant is primarily metabolized by cytochrome-P450 3A4 enzyme (CYP3A4) with a minor contribution from CYP2C19. Major circulating metabolites are suvorexant and a hydroxy-suvorexant metabolite, which is not expected to be pharmacologically active. There is potential for drug-drug interactions with drugs that inhibit or induce CYP3A4 activity.
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- Route of elimination
Approximately 66% is eliminated in feces and 23% is eliminated in urine.
- Half-life
Mean half life is approximately 12 hours.
- Clearance
Not Available
- Adverse Effects
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Dose-related somnolence and CNS depression are the most common adverse effects associated with the use of suvorexant. It has also been shown to impair driving skills and may increase the risk of falling asleep while driving. Next-day impairments are found to be highest if suvorexant is taken with less than a full night of sleep remaining, with higher doses, or if co-administered with other CNS depressants or CYP3A inhibitors. Complex behaviours such as sleep driving, preparing and eating food, and making phone calls have been reported in association with the use of hypnotics such as suvorexant. A dose-dependant increase in suicidal ideation has been observed, especially in patients with a previous diagnosis of depression. Sleep paralysis, hypnagogic/hypnopompic hallucinations including vivid and disturbing perceptions, and mild cataplexy have also been reported. There are no adequate studies in pregnant women to ensure its safety during pregnancy or breast feeding.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine 1,2-Benzodiazepine may increase the central nervous system depressant (CNS depressant) activities of Suvorexant. Abametapir The serum concentration of Suvorexant can be increased when it is combined with Abametapir. Abatacept The metabolism of Suvorexant can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Suvorexant. Acalabrutinib The metabolism of Acalabrutinib can be decreased when combined with Suvorexant. Acenocoumarol The metabolism of Acenocoumarol can be decreased when combined with Suvorexant. Acetaminophen The metabolism of Suvorexant can be increased when combined with Acetaminophen. Acetazolamide Acetazolamide may increase the central nervous system depressant (CNS depressant) activities of Suvorexant. Acetophenazine Acetophenazine may increase the central nervous system depressant (CNS depressant) activities of Suvorexant. Adagrasib The metabolism of Suvorexant can be decreased when combined with Adagrasib. 
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- Avoid grapefruit products.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Belsomra Tablet, film coated 10 mg/1 Oral Merck Sharp & Dohme Llc 2014-08-29 Not applicable US 
Belsomra Tablet 20 mg Oral Merck Ltd. 2019-04-18 2020-05-14 Canada 
Belsomra Tablet, film coated 20 mg/1 Oral Merck Sharp & Dohme Llc 2014-08-29 Not applicable US Belsomra Tablet, film coated 5 mg/1 Oral Merck Sharp & Dohme Llc 2014-08-29 Not applicable US Belsomra Tablet 15 mg Oral Merck Ltd. 2019-04-18 2020-05-14 Canada Belsomra Tablet, film coated 15 mg/1 Oral Merck Sharp & Dohme Llc 2014-08-29 Not applicable US Belsomra Tablet 5 mg Oral Merck Ltd. Not applicable Not applicable Canada Belsomra Tablet 10 mg Oral Merck Ltd. 2019-04-18 2020-05-14 Canada
Categories
- ATC Codes
- N05CM19 — Suvorexant
- Drug Categories
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Hypnotics and Sedatives
- Miscellaneous Anxiolytics Sedatives and Hypnotics
- Nervous System
- Neurotransmitter Agents
- Orexin Receptor Antagonists
- P-glycoprotein inhibitors
- Psycholeptics
- Sleep Aids, Pharmaceutical
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as n,n-dialkyl-m-toluamides. These are aromatic that contain a m-toluamide, where the carboxamide group is N- substituted with two alkyl chains.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Toluenes
- Direct Parent
- N,N-dialkyl-m-toluamides
- Alternative Parents
- Phenyl-1,2,3-triazoles / Benzamides / Benzoxazoles / Dialkylarylamines / Benzoyl derivatives / 1,4-diazepanes / Aryl chlorides / Tertiary carboxylic acid amides / Oxazoles / Heteroaromatic compounds show 7 more
- Substituents
- 1,2,3-triazole / 1,4-diazepane / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Azole / Benzamide / Benzoic acid or derivatives / Benzoxazole show 23 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- 1,3-benzoxazoles, organochlorine compound, aromatic amide, triazoles, diazepine (CHEBI:82698)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 081L192FO9
- CAS number
- 1030377-33-3
- InChI Key
- JYTNQNCOQXFQPK-MRXNPFEDSA-N
- InChI
- InChI=1S/C23H23ClN6O2/c1-15-3-5-20(30-25-8-9-26-30)18(13-15)22(31)29-12-11-28(10-7-16(29)2)23-27-19-14-17(24)4-6-21(19)32-23/h3-6,8-9,13-14,16H,7,10-12H2,1-2H3/t16-/m1/s1
- IUPAC Name
- 5-chloro-2-[(5R)-5-methyl-4-[5-methyl-2-(2H-1,2,3-triazol-2-yl)benzoyl]-1,4-diazepan-1-yl]-1,3-benzoxazole
- SMILES
- [H][C@@]1(C)CCN(CCN1C(=O)C1=C(C=CC(C)=C1)N1N=CC=N1)C1=NC2=C(O1)C=CC(Cl)=C2
References
- General References
- Palasz A, Lapray D, Peyron C, Rojczyk-Golebiewska E, Skowronek R, Markowski G, Czajkowska B, Krzystanek M, Wiaderkiewicz R: Dual orexin receptor antagonists - promising agents in the treatment of sleep disorders. Int J Neuropsychopharmacol. 2014 Jan;17(1):157-68. doi: 10.1017/S1461145713000552. Epub 2013 May 23. [Article]
- Patel KV, Aspesi AV, Evoy KE: Suvorexant: a dual orexin receptor antagonist for the treatment of sleep onset and sleep maintenance insomnia. Ann Pharmacother. 2015 Apr;49(4):477-83. doi: 10.1177/1060028015570467. Epub 2015 Feb 9. [Article]
- Reddy A, Puvvada SC, Kommisetti S, El-Mallakh RS, Lippmann S: Suvorexant: something new for sleep? Acta Neuropsychiatr. 2015 Feb;27(1):53-5. doi: 10.1017/neu.2014.31. Epub 2014 Nov 14. [Article]
- Michelson D, Snyder E, Paradis E, Chengan-Liu M, Snavely DB, Hutzelmann J, Walsh JK, Krystal AD, Benca RM, Cohn M, Lines C, Roth T, Herring WJ: Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: a phase 3 randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2014 May;13(5):461-71. doi: 10.1016/S1474-4422(14)70053-5. Epub 2014 Mar 27. [Article]
- Howland RH: Suvorexant: a novel therapy for the treatment of insomnia. J Psychosoc Nurs Ment Health Serv. 2014 Oct;52(10):23-6. doi: 10.3928/02793695-20140924-01. [Article]
- FDA Approved Drug Products: BELSOMRA (suvorexant) tablets [Link]
- External Links
- KEGG Drug
- D10082
- PubChem Compound
- 24965990
- PubChem Substance
- 310264985
- ChemSpider
- 24662178
- BindingDB
- 50318701
- 1547099
- ChEBI
- 82698
- ChEMBL
- CHEMBL1083659
- ZINC
- ZINC000049036447
- PDBe Ligand
- SUV
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Suvorexant
- PDB Entries
- 4s0v / 4zj8 / 6to7 / 6tpj
- FDA label
- Download (403 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Basic Science Panic Disorder 1 4 Completed Treatment Bipolar Disorder (BD) / Insomnia 1 4 Completed Treatment Fatigue / Insomnia / Multiple Sclerosis 1 4 Completed Treatment Hypertension / Insomnia 1 4 Completed Treatment Inflammation / Insomnia / Sleep disorders and disturbances / Type 2 Diabetes Mellitus 1 4 Completed Treatment Insomnia 3 4 Completed Treatment Insomnia / Post Traumatic Stress Disorder (PTSD) 1 4 Completed Treatment Post Traumatic Stress Disorder (PTSD) 1 4 Completed Treatment Shift-work related sleep disturbance 1 4 Recruiting Basic Science Insomnia Chronic 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 10 mg Tablet Oral 15 mg Tablet Oral 20 mg Tablet Oral 5 mg Tablet, film coated Oral 10 mg/1 Tablet, film coated Oral 15 mg/1 Tablet, film coated Oral 20 mg/1 Tablet, film coated Oral 5 mg/1 Tablet, coated Oral 10 mg Tablet, coated Oral 15 mg Tablet, coated Oral 20 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US20110195957 No 2011-04-19 2031-04-19 US US7951797 No 2011-05-31 2029-11-20 US US10098892 No 2018-10-16 2033-05-29 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.117 mg/mL ALOGPS logP 3.86 ALOGPS logP 4.04 Chemaxon logS -3.6 ALOGPS pKa (Strongest Basic) 0.25 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 80.29 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 134.36 m3·mol-1 Chemaxon Polarizability 46.68 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Peptide hormone binding
- Specific Function
- Moderately selective excitatory receptor for orexin-A and, with a lower affinity, for orexin-B neuropeptide. Seems to be exclusively coupled to the G(q) subclass of heteromeric G proteins, which ac...
- Gene Name
- HCRTR1
- Uniprot ID
- O43613
- Uniprot Name
- Orexin receptor type 1
- Molecular Weight
- 47535.33 Da
References
- Palasz A, Lapray D, Peyron C, Rojczyk-Golebiewska E, Skowronek R, Markowski G, Czajkowska B, Krzystanek M, Wiaderkiewicz R: Dual orexin receptor antagonists - promising agents in the treatment of sleep disorders. Int J Neuropsychopharmacol. 2014 Jan;17(1):157-68. doi: 10.1017/S1461145713000552. Epub 2013 May 23. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Peptide hormone binding
- Specific Function
- Nonselective, high-affinity receptor for both orexin-A and orexin-B neuropeptides.
- Gene Name
- HCRTR2
- Uniprot ID
- O43614
- Uniprot Name
- Orexin receptor type 2
- Molecular Weight
- 50693.965 Da
References
- Palasz A, Lapray D, Peyron C, Rojczyk-Golebiewska E, Skowronek R, Markowski G, Czajkowska B, Krzystanek M, Wiaderkiewicz R: Dual orexin receptor antagonists - promising agents in the treatment of sleep disorders. Int J Neuropsychopharmacol. 2014 Jan;17(1):157-68. doi: 10.1017/S1461145713000552. Epub 2013 May 23. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Lee-Iannotti JK, Parish JM: Suvorexant: a promising, novel treatment for insomnia. Neuropsychiatr Dis Treat. 2016 Feb 25;12:491-5. doi: 10.2147/NDT.S31495. eCollection 2016. [Article]
- Rhyne DN, Anderson SL: Suvorexant in insomnia: efficacy, safety and place in therapy. Ther Adv Drug Saf. 2015 Oct;6(5):189-95. doi: 10.1177/2042098615595359. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- Molecular Weight
- 141477.255 Da
Drug created at February 23, 2015 22:11 / Updated at March 19, 2023 23:50