Solriamfetol

Last updated

Solriamfetol
Solriamfetol.svg
Clinical data
Trade names Sunosi
Other namesSKL-N05, ADX-N05, ARL-N05, YKP10A, R228060, and JZP-110; (R)-2-amino-3-phenylpropylcarbamate; O-Carbamoyl-D-phenylalaninol
AHFS/Drugs.com Monograph
MedlinePlus a619040
License data
Routes of
administration 		By mouth [1]
Drug class Norepinephrine–dopamine reuptake inhibitors; Wakefulness-promoting agents; Psychostimulants
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability ~95% [1]
Protein binding 13.3–19.4% [1]
Metabolism Minimal (~1%) [1]
Metabolites • N-Acetylsolriamfetol (~1%) [1]
Elimination half-life ~7.1 hours [1]
Excretion Urine (95% unchanged)
Identifiers
  • (2R)-2-Amino-3-phenylpropyl carbamate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C10H14N2O2
Molar mass 194.234 g·mol−1
3D model (JSmol)
  • C1=CC=C(C=C1)C[C@H](COC(=O)N)N
  • InChI=1S/C10H14N2O2/c11-9(7-14-10(12)13)6-8-4-2-1-3-5-8/h1-5,9H,6-7,11H2,(H2,12,13)/t9-/m1/s1
  • Key:UCTRAOBQFUDCSR-SECBINFHSA-N

Solriamfetol, sold under the brand name Sunosi, is a wakefulness-promoting medication used in the treatment of excessive sleepiness related to narcolepsy and sleep apnea. [1] [5] [6] It is taken by mouth. [1]

Contents

Common side effects of solriamfetol include headache, nausea, anxiety, and trouble sleeping. [1] It is a norepinephrine–dopamine reuptake inhibitor (NDRI) and is thought to work by increasing levels of the neurotransmitters norepinephrine and dopamine in the brain. [1] [5] Solriamfetol has also been found to act as a TAAR1 agonist, an action that may also be involved in its effects. [7]

The drug was discovered by a subsidiary of SK Group, which licensed rights outside of eleven countries in Asia to Aerial Pharma in 2011. [8] In addition to its approved indication of excessive sleepiness, solriamfetol is under development for certain other uses including the treatment of attention deficit hyperactivity disorder (ADHD), binge eating disorder, and circadian rhythm sleep disorders. [9]

Medical uses

Solriamfetol is used to promote wakefulness in the treatment of excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea in adults. [1] It appears to be more effective in improving excessive daytime sleepiness associated with obstructive sleep apnea than certain other wakefulness-promoting agents including modafinil, armodafinil, and pitolisant. [10]

Available forms

Solriamfetol is available in the form of 75 and 150 mg oral tablets. [1]

Side effects

Side effects of solriamfetol include headache, nausea, decreased appetite, insomnia, anxiety, irritability, feeling jittery, dizziness, chest discomfort, heart palpitations, dry mouth, increased sweating, abdominal pain, constipation, and diarrhea. [1]

Misuse potential

Solriamfetol at higher-than-approved doses—specifically doses of 300, 600, and 1,200 mg, which are 2 to 4 times the maximum recommended dose—produces drug-liking responses, including elevated mood and feelings of relaxation, that are similar in degree to those of phentermine (a Schedule IV controlled substance). [1] Elevated mood occurred in 2.4% with placebo, 8 to 24% with solriamfetol, and 10 to 18% with phentermine, while feelings of relaxation occurred in 5% with placebo, 5 to 19% with solriamfetol, and 15 to 20% with phentermine. [1] As such, solriamfetol has significant misuse potential and is a controlled substance in the United States. [1] However, solriamfetol showed less misuse potential than Schedule II controlled stimulants like amphetamine and cocaine. [11] Consequently, the misuse potential of solriamfetol was rated as low and it was placed in the Schedule IV controlled substance category alongside phentermine. [11]

Pharmacology

Pharmacodynamics

Solriamfetol is a norepinephrine–dopamine reuptake inhibitor (NDRI). [1] It binds to the dopamine transporter (DAT) and the norepinephrine transporter (NET) with affinities (Ki) of 14.2 μM and 3.7 μM, respectively. [1] It inhibits the reuptake of dopamine and norepinephrine with IC50 values of 2.9 μM and 4.4 μM, respectively. [1] It has weak affinity for the serotonin transporter (Ki = 81.5 μM) and does not appreciably inhibit serotonin reuptake (IC50 > 100 μM). [1] In addition to its dopamine and norepinephrine reuptake inhibition, solriamfetol has been found to act as an agonist of the human and rodent TAAR1 (EC50 = 10–16 μM) at clinically relevant concentrations similar to those of its DAT and NET inhibition. [7] Solriamfetol has no appreciable affinity for a variety of other targets, including the dopamine, serotonin, adrenergic, GABA, adenosine, histamine, orexin, benzodiazepine, and acetylcholine receptors. [1]

Pharmacokinetics

The oral bioavailability of solriamfetol is approximately 95%. [1] The median time to peak levels of solriamfetol is 2 hours, with a range of 1.25 to 3.0 hours. [1] A high-fat meal has minimal influence on the peak and total concentrations of solriamfetol, but does delay time to peak levels by approximately 1 hour. [1] The apparent volume of distribution of solriamfetol is approximately 199 L. [1] The plasma protein binding of solriamfetol is 13.3% to 19.4% over a concentration range of 0.059 to 10.1 μg/mL. [1] Solriamfetol is minimally metabolized in humans. [1] It shows first-order elimination with oral administration and has an elimination half-life of about 7.1 hours. [1] The half-life of solriamfetol increases in the context of renal impairment. [1] Approximately 95% of a dose of solriamfetol is eliminated in urine as unchanged solriamfetol and 1% or less is eliminated as the minor inactive metabolite N-acetylsolriamfetol. [1]

Chemistry

Solriamfetol is a substituted phenethylamine derived from d-phenylalanine and D-phenylalaninol. [12] Its chemical name is (R)-2-amino-3-phenylpropylcarbamate. [13] [12] It is also known as O-carbamoyl-D-phenylalaninol. [13]

History

The drug was discovered by a subsidiary of SK Group, which licensed rights outside of eleven countries in Asia to Aerial Pharma in 2011. [8] Aerial ran two Phase II trials of the drug in narcolepsy [14] before selling the license to solriamfetol to Jazz in 2014; Jazz Pharmaceuticals paid Aerial $125 million up front and will pay Aerial and SK up to $272 million in milestone payments, and will pay double-digit royalties to SK. [8] [15]

In 2019, solriamfetol was approved in the United States to improve wakefulness in adults with narcolepsy or obstructive sleep apnea (OSA). [16] [17] It was granted orphan drug designation. [18]

The U.S. Food and Drug Administration (FDA) approved solriamfetol based primarily on evidence from five clinical trials (Trial 1/NCT02348593, Trial 2/NCT02348606, Trial 3/NCT02348619, Trial 4/NCT02348632, Trial 5 NCT01681121) of 622 patients with narcolepsy or obstructive sleep apnea (OSA). [16] The trials were conducted in Canada, Europe, and the United States. [16]

Solriamfetol was approved for medical use in the European Union in January 2020. [4]

In March 2022, it was announced that Axsome Therapeutics would be acquiring Solriamfetol, under the brand name Sunosi, from Jazz Pharmaceuticals, for an upfront sum of $53 million. Jazz will receive a high single-digit royalty on Axsome's U.S. net sales of Sunosi in the current indication, and a mid-single-digit royalty in the future indications. Axsome will also assume the commitments of Jazz to SK Biopharmaceuticals and Aerial Biopharma. [19]

Society and culture

Names

During development it has been called SKL-N05, ADX-N05, ARL-N05, and JZP-110. [9]

In the United States, solriamfetol is a Schedule IV controlled substance, [1] meaning that it has an accepted medical use and a low potential for abuse, but that abuse may lead to physical or psychological dependence. [20] A prescription is required, and can only be refilled up to five times in a six-month period. [21] In countries of the European Union, a prescription is required. [4]

Research

Solriamfetol is under development for the treatment of attention deficit hyperactivity disorder (ADHD), binge eating disorder, and circadian rhythm sleep disorders. [9] [22] As of September 2023, it is in phase 3 clinical trials for ADHD and phase 2 clinical trials for binge eating disorder and circadian rhythm sleep disorders. [9] [22] A case report of solriamfetol for the treatment of ADHD has been published. [23] Solriamfetol was also under development for the treatment of depressive disorders, but development for this indication was discontinued. [9] In May 2024, the National Institutes of Health (NIH) announced a trial of solriamfetol for the treatment of long COVID. [24]

Related Research Articles

<span class="mw-page-title-main">Modafinil</span> Eugeroic medication

Modafinil, sold under the brand name Provigil among others, is a central nervous system (CNS) stimulant and eugeroic medication used primarily to treat narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and sudden sleep attacks. Modafinil is also approved for stimulating wakefulness in people with sleep apnea and shift work sleep disorder. It is taken by mouth. Modafinil is not approved by the US Food and Drug Administration (FDA) for use in people under 17 years old.

<span class="mw-page-title-main">Adderall</span> Drug mixture used mainly to treat ADHD and narcolepsy

Adderall and Mydayis are trade names for a combination drug containing four salts of amphetamine. The mixture is composed of equal parts racemic amphetamine and dextroamphetamine, which produces a (3:1) ratio between dextroamphetamine and levoamphetamine, the two enantiomers of amphetamine. Both enantiomers are stimulants, but differ enough to give Adderall an effects profile distinct from those of racemic amphetamine or dextroamphetamine, which are marketed as Evekeo and Dexedrine/Zenzedi, respectively. Adderall is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. It is also used illicitly as an athletic performance enhancer, cognitive enhancer, appetite suppressant, and recreationally as a euphoriant. It is a central nervous system (CNS) stimulant of the phenethylamine class.

A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopamine not absorbed by the postsynaptic neuron is blocked from re-entering the presynaptic neuron. This results in increased extracellular concentrations of dopamine and increase in dopaminergic neurotransmission.

Hypersomnia is a neurological disorder of excessive time spent sleeping or excessive sleepiness. It can have many possible causes and can cause distress and problems with functioning. In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), hypersomnolence, of which there are several subtypes, appears under sleep-wake disorders.

A microsleep is a sudden temporary episode of sleep or drowsiness which may last for a few seconds where an individual fails to respond to some arbitrary sensory input and becomes unconscious. Episodes of microsleep occur when an individual loses and regains awareness after a brief lapse in consciousness, often without warning, or when there are sudden shifts between states of wakefulness and sleep. In behavioural terms, microsleeps may manifest as droopy eyes, slow eyelid-closure, and head nodding. In electrical terms, microsleeps are often classified as a shift in electroencephalography (EEG) during which 4–7 Hz activity replaces the waking 8–13 Hz background rhythm.

<span class="mw-page-title-main">Armodafinil</span> Eugeroic medication

Armodafinil, sold under the brand name Nuvigil, is a wakefulness-promoting medication which is used to treat excessive daytime sleepiness associated with obstructive sleep apnea, narcolepsy, and shift work disorder. It is also used off-label for certain other indications. The drug is taken by mouth.

Excessive daytime sleepiness (EDS) is characterized by persistent sleepiness and often a general lack of energy, even during the day after apparently adequate or even prolonged nighttime sleep. EDS can be considered as a broad condition encompassing several sleep disorders where increased sleep is a symptom, or as a symptom of another underlying disorder like narcolepsy, circadian rhythm sleep disorder, sleep apnea or idiopathic hypersomnia.

<span class="mw-page-title-main">TAAR1</span> Protein-coding gene in the species Homo sapiens

Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the TAAR1 gene.

<span class="mw-page-title-main">Levoamphetamine</span> CNS stimulant and isomer of amphetamine

Levoamphetamine is a stimulant medication which is used in the treatment of certain medical conditions. It was previously marketed by itself under the brand name Cydril, but is now available only in combination with dextroamphetamine in varying ratios under brand names like Adderall and Evekeo. The drug is known to increase wakefulness and concentration in association with decreased appetite and fatigue. Pharmaceuticals that contain levoamphetamine are currently indicated and prescribed for the treatment of attention deficit hyperactivity disorder (ADHD), obesity, and narcolepsy in some countries. Levoamphetamine is taken by mouth.

<span class="mw-page-title-main">Narcolepsy</span> Human sleep disorder

Narcolepsy is a chronic neurological disorder that impairs the ability to regulate sleep–wake cycles, and specifically impacts REM sleep. The pentad symptoms of narcolepsy include excessive daytime sleepiness (EDS), sleep-related hallucinations, sleep paralysis, disturbed nocturnal sleep (DNS), and cataplexy. People with narcolepsy tend to sleep about the same number of hours per day as people without it, but the quality of sleep is typically compromised.

Pitolisant, sold under the brand name Wakix among others, is a medication used for the treatment of excessive daytime sleepiness in adults with narcolepsy. It is an inverse agonist of the histamine H3 receptor. It represents the first commercially available medication in its class, so that the U.S. Food and Drug Administration (FDA) declares it a first-in-class medication. Pitolisant enhances the activity of histaminergic neurons in the brain that function to improve a person's wakefulness. It was approved by the European Medicines Agency (EMA) in March 2016 for narcolepsy with or without cataplexy, and for excessive daytime sleepiness by the FDA in August 2019. The most common side effects include difficulty sleeping, nausea, and feeling worried.

<span class="mw-page-title-main">Norepinephrine releasing agent</span> Catecholaminergic type of drug

A norepinephrine releasing agent (NRA), also known as an adrenergic releasing agent, is a catecholaminergic type of drug that induces the release of norepinephrine (noradrenaline) and epinephrine (adrenaline) from the pre-synaptic neuron into the synapse. This in turn leads to increased extracellular concentrations of norepinephrine and epinephrine therefore an increase in adrenergic neurotransmission.

<span class="mw-page-title-main">Dopamine releasing agent</span> Type of drug

A dopamine releasing agent (DRA) is a type of drug which induces the release of dopamine in the body and/or brain.

<span class="mw-page-title-main">Eugeroic</span> Drug for wakefulness and alertness

A eugeroic, or eugregoric, is a type of drug that increases wakefulness. The term has been used inconsistently and in multiple ways in the scientific literature, either to refer specifically to modafinil-type wakefulness-promoting agents or to refer to wakefulness-promoting agents generally. It was first introduced in the French literature in 1987 as a descriptor for modafinil-like wakefulness-promoting drugs and for purposes of distinguishing such drugs from psychostimulants. However, the term "eugeroic" has not been widely adopted in the literature, and instead the term "wakefulness-promoting agent" has been more widely used, both for modafinil-type drugs and other agents.

<span class="mw-page-title-main">Norepinephrine–dopamine reuptake inhibitor</span> Drug that inhibits the reuptake of norepinephrine and dopamine

A norepinephrine–dopamine reuptake inhibitor (NDRI) is a drug used for the treatment of clinical depression, attention deficit hyperactivity disorder (ADHD), narcolepsy, and the management of Parkinson's disease. The drug acts as a reuptake inhibitor for the neurotransmitters norepinephrine and dopamine by blocking the action of the norepinephrine transporter (NET) and the dopamine transporter (DAT), respectively. This in turn leads to increased extracellular concentrations of both norepinephrine and dopamine and, therefore, an increase in adrenergic and dopaminergic neurotransmission.

Idiopathic hypersomnia (IH) is a neurological disorder which is characterized primarily by excessive sleep and excessive daytime sleepiness (EDS). Idiopathic hypersomnia was first described by Bedrich Roth in 1976, and it can be divided into two forms: polysymptomatic and monosymptomatic. The condition typically becomes evident in early adulthood and most patients diagnosed with IH will have had the disorder for many years prior to their diagnosis. As of August 2021, an FDA-approved medication exists for IH called Xywav, which is an oral solution of calcium, magnesium, potassium, and sodium oxybates; in addition to several off-label treatments.

<span class="mw-page-title-main">Wakefulness-promoting agent</span> Drug that increases wakefulness

A wakefulness-promoting agent (WPA), or wake-promoting agent, is a drug that increases wakefulness and arousal. They are similar to but distinct from psychostimulants, which not only promote wakefulness but also produce other more overt central nervous system effects, such as improved attention span, executive functions, vigilance and motivation. Wakefulness-promoting agents are used to treat narcolepsy and hypersomnia as well as to promote wakefulness and increase performance in healthy people.

<span class="mw-page-title-main">Phenylalaninol</span> Pharmaceutical compound

Phenylalaninol, or DL-phenylalaninol, also known as phenylmethylethanolamine or as α-(hydroxymethyl)phenethylamine, is a psychostimulant and monoamine releasing agent (MRA) of the phenethylamine family. It is related to the amino acid phenylalanine and to the phenethylamine psychostimulants β-phenethylamine (phenylethylamine) and amphetamine (α-methylphenethylamine).

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 "Sunosi – solriamfetol tablet, film coated". DailyMed . 16 October 2019. Retrieved 24 November 2019.
  2. ↑ "Summary Basis of Decision (SBD) for Sunosi". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  3. ↑ "Health product highlights 2021: Annexes of products approved in 2021". Health Canada . 3 August 2022. Retrieved 25 March 2024.
  4. 1 2 3 "Sunosi EPAR". European Medicines Agency (EMA). 12 November 2019. Retrieved 26 September 2020.
  5. 1 2 Powell J, Piszczatoski C, Garland S (October 2020). "Solriamfetol for Excessive Sleepiness in Narcolepsy and Obstructive Sleep Apnea". Ann Pharmacother. 54 (10): 1016–1020. doi:10.1177/1060028020915537. PMID   32270686. S2CID   215605290.
  6. ↑ Abad VC, Guilleminault C (December 2018). "Solriamfetol for the treatment of daytime sleepiness in obstructive sleep apnea". Expert Rev Respir Med. 12 (12): 1007–1019. doi:10.1080/17476348.2018.1541742. PMID   30365900. S2CID   53106520.
  7. 1 2 Gursahani H, Jolas T, Martin M, Cotier S, Hughes S, Macfadden W, et al. (2023). "Preclinical Pharmacology of Solriamfetol: Potential Mechanisms for Wake Promotion". CNS Spectrums. 28 (2): 222. doi:10.1017/S1092852923001396. ISSN   1092-8529. In vitro functional studies showed agonist activity of solriamfetol at human, mouse, and rat TAAR1 receptors. hTAAR1 EC50 values (10–16 μM) were within the clinically observed therapeutic solriamfetol plasma concentration range and overlapped with the observed DAT/NET inhibitory potencies of solriamfetol in vitro. TAAR1 agonist activity was unique to solriamfetol; neither the WPA modafinil nor the DAT/NET inhibitor bupropion had TAAR1 agonist activity.
  8. 1 2 3 Ji-young S (5 March 2018). "SK Biopharmaceuticals' narcolepsy drug on track to hitting US market". The Korea Herald.
  9. 1 2 3 4 5 "Solriamfetol – Jazz Pharmaceuticals/SK Biopharmaceuticals". AdisInsight. Retrieved 13 October 2023.
  10. ↑ Pitre T, Mah J, Roberts S, Desai K, Gu Y, Ryan C, et al. (May 2023). "Comparative Efficacy and Safety of Wakefulness-Promoting Agents for Excessive Daytime Sleepiness in Patients With Obstructive Sleep Apnea : A Systematic Review and Network Meta-analysis". Ann Intern Med. 176 (5): 676–684. doi:10.7326/M22-3473. PMID   37155992. S2CID   258558603.
  11. 1 2 "Federal Register :: Request Access". 17 June 2019.
  12. 1 2 Abad VC, Guilleminault C (2017). "New developments in the management of narcolepsy". Nature and Science of Sleep. 9: 39–57. doi: 10.2147/NSS.S103467 . PMC   5344488 . PMID   28424564.
  13. 1 2 "Solriamfetol". PubChem. Retrieved 15 January 2025.
  14. ↑ Sullivan SS, Guilleminault C (2015). "Emerging drugs for common conditions of sleepiness: obstructive sleep apnea and narcolepsy". Expert Opinion on Emerging Drugs. 20 (4): 571–82. doi:10.1517/14728214.2015.1115480. PMID   26558298. S2CID   7951307.
  15. ↑ Garde D (14 January 2014). "Jazz bets up to $397M on Aerial's narcolepsy drug". FierceBiotech.
  16. 1 2 3 "Drug Trials Snapshots: Sunosi". U.S. Food and Drug Administration (FDA). 16 April 2019. Archived from the original on 28 September 2019. Retrieved 24 November 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  17. ↑ "Drug Approval Package: Sunosi". U.S. Food and Drug Administration (FDA). 29 April 2019. Retrieved 24 November 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  18. ↑ "Solriamfetol Orphan Drug Approval". U.S. Food and Drug Administration (FDA). Retrieved 24 November 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  19. ↑ "Axsome To Buy Sunosi From Jazz". NASDAQ . Retrieved 28 March 2022.
  20. ↑ 21 U.S.C.   § 812 – Schedules of controlled substances
  21. ↑ "Manuals – Practitioner's Manual – Section V". Archived from the original on 7 January 2014. Retrieved 30 May 2021. Retrieved 2014-01-07
  22. 1 2 Surman CB, Walsh DM, Horick N, DiSalvo M, Vater CH, Kaufman D (October 2023). "Solriamfetol for Attention-Deficit/Hyperactivity Disorder in Adults: A Double-Blind Placebo-Controlled Pilot Study". J Clin Psychiatry. 84 (6). doi:10.4088/JCP.23m14934. PMID   37819836. S2CID   263715808.
  23. ↑ Naguy A, El-Sheshaie A, Elsori DH, Alamiri B (April 2021). "Solriamfetol for attention deficit hyperactivity disorder". CNS Spectr. 27 (6): 662–663. doi: 10.1017/S1092852921000328 . PMID   33870884.
  24. ↑ "NIH to open long COVID clinical trials to study sleep disturbances, exercise intolerance, and post exertional malaise". National Institutes of Health (NIH). 7 May 2024. Retrieved 2 August 2024.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.