Clinical data | |
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Trade names | Sunosi |
Other names | SKL-N05, ADX-N05, ARL-N05, YKP10A, R228060, and JZP-110; (R)-2-amino-3-phenylpropylcarbamate hydrochloride |
AHFS/Drugs.com | Monograph |
MedlinePlus | a619040 |
License data |
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Routes of administration | By mouth |
Drug class | Norepinephrine–dopamine reuptake inhibitors |
ATC code | |
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Pharmacokinetic data | |
Bioavailability | ~95% [3] |
Protein binding | 13.3–19.4% [3] |
Metabolism | Minimal [3] |
Elimination half-life | ~7.1 hours [3] |
Excretion | Urine (95% unchanged) |
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IUPHAR/BPS | |
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Chemical and physical data | |
Formula | C10H14N2O2 |
Molar mass | 194.234 g·mol−1 |
3D model (JSmol) | |
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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. [3] [5] [6] It is taken by mouth. [3]
Common side effects of solriamfetol include headache, nausea, anxiety, and trouble sleeping. [3] 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. [3] [5]
The drug was discovered by a subsidiary of SK Group, which licensed rights outside of eleven countries in Asia to Aerial Pharma in 2011. [7] 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. [8]
Solriamfetol is used to promote wakefulness in the treatment of excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea in adults. [3] 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. [9]
Solriamfetol is available in the form of 75 and 150 mg oral tablets. [3]
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. [3]
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). [3] 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. [3] As such, solriamfetol has significant misuse potential and is a controlled substance in the United States. [3] However, solriamfetol showed less misuse potential than Schedule II controlled stimulants like amphetamine and cocaine. [10] Consequently, the misuse potential of solriamfetol was rated as low and it was placed in the Schedule IV controlled substance category alongside phentermine. [10]
Solriamfetol is a norepinephrine–dopamine reuptake inhibitor (NDRI). [3] It binds to the dopamine transporter and the norepinephrine transporter with affinities (Ki) of 14.2 μM and 3.7 μM, respectively. [3] It inhibits the reuptake of dopamine and norepinephrine with IC50 values of 2.9 μM and 4.4 μM, respectively. [3] It has weak affinity for the serotonin transporter (Ki = 81.5 μM) and does not appreciably inhibit serotonin reuptake (IC50 > 100 μM). [3] Solriamfetol has no appreciable affinity for a variety of other targets, including the dopamine, serotonin, adrenergic, GABA, adenosine, histamine, orexin, benzodiazepine, and acetylcholine receptors. [3]
The oral bioavailability of solriamfetol is approximately 95%. [3] The median time to peak levels of solriamfetol is 2 hours, with a range of 1.25 to 3.0 hours. [3] 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. [3] The apparent volume of distribution of solriamfetol is approximately 199 L. [3] The plasma protein binding of solriamfetol is 13.3% to 19.4% over a concentration range of 0.059 to 10.1 μg/mL. [3] Solriamfetol is minimally metabolized in humans. [3] It shows first-order elimination with oral administration and has an elimination half-life of about 7.1 hours. [3] The half-life of solriamfetol increases in the context of renal impairment. [3] 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. [3]
Solriamfetol is derived from d-phenylalanine and its chemical name is (R)-2-amino-3-phenylpropylcarbamate. [11]
The drug was discovered by a subsidiary of SK Group, which licensed rights outside of eleven countries in Asia to Aerial Pharma in 2011. [7] Aerial ran two Phase II trials of the drug in narcolepsy [12] 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. [7] [13]
In 2019, solriamfetol was approved in the United States to improve wakefulness in adults with narcolepsy or obstructive sleep apnea (OSA). [14] [15] It was granted orphan drug designation. [16]
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). [14] The trials were conducted in Canada, Europe, and the United States. [14]
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. [17]
During development it has been called SKL-N05, ADX-N05, ARL-N05, and JZP-110. [8]
In the United States, solriamfetol is a Schedule IV controlled substance, [3] meaning that it has an accepted medical use and a low potential for abuse, but that abuse may lead to physical or psychological dependence. [18] A prescription is required, and can only be refilled up to five times in a six-month period. [19] In countries of the European Union, a prescription is required. [4]
Solriamfetol is under development for the treatment of attention deficit hyperactivity disorder (ADHD), binge eating disorder, and circadian rhythm sleep disorders. [8] [20] 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. [8] [20] A case report of solriamfetol for the treatment of ADHD has been published. [21] Solriamfetol was also under development for the treatment of depressive disorders, but development for this indication was discontinued. [8] In May 2024 the NIH announced a trial of solriamfetol for the treatment of long covid.
Modafinil, sold under the brand name Provigil among others, is a wakefulness-promoting medication used primarily to treat narcolepsy. 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 age 17.
Methylphenidate, sold under the brand names Ritalin and Concerta among others, is a potent central nervous system (CNS) stimulant used medically to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, narcolepsy. It is a primary medication for ADHD ; it may be taken by mouth or applied to the skin, and different formulations have varying durations of effect, commonly ranging from 2-4 hours. For ADHD, the effectiveness of methylphenidate is comparable to atomoxetine but modestly lower than amphetamines.
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.
Upper airway resistance syndrome (UARS) is a sleep disorder characterized by the narrowing of the airway that can cause disruptions to sleep. The symptoms include unrefreshing sleep, fatigue, sleepiness, chronic insomnia, and difficulty concentrating. UARS can be diagnosed by polysomnograms capable of detecting Respiratory Effort-related Arousals. It can be treated with lifestyle changes, functional orthodontics, surgery, mandibular repositioning devices or CPAP therapy. UARS is considered a variant of sleep apnea, although some scientists and doctors believe it to be a distinct disorder.
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, MSs 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.
Pemoline, sold under the brand name Cylert among others, is a stimulant medication which has been used in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy. It has been discontinued in most countries due to rare but serious problems with liver toxicity. The medication was taken by mouth.
Viloxazine, sold under the brand name Qelbree and formerly as Vivalan among others, is a selective norepinephrine reuptake inhibitor medication which is used in the treatment of attention deficit hyperactivity disorder (ADHD) in children and adults. It was marketed for almost 30 years as an antidepressant for the treatment of depression before being discontinued and subsequently repurposed as a treatment for ADHD. Viloxazine is taken orally. It was used as an antidepressant in an immediate-release form and is used in ADHD in an extended-release form.
Armodafinil (trade name Nuvigil) is the enantiopure compound of the eugeroic modafinil (Provigil). It consists of only the (R)-(−)-enantiomer of the racemic modafinil. Armodafinil is produced by the pharmaceutical company Cephalon Inc. and was approved by the U.S. Food and Drug Administration (FDA) in June 2007. In 2016, the FDA granted Mylan rights for the first generic version of Cephalon's Nuvigil to be marketed in the U.S.
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.
Christian Guilleminault was a French physician and researcher in the field of sleep medicine who played a central role in the early discovery of obstructive sleep apnea and made seminal discoveries in many other areas of sleep medicine.
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. There are two recognized forms of narcolepsy, narcolepsy type 1 and type 2. Narcolepsy type 1 (NT1) can be clinically characterized by symptoms of EDS and cataplexy, and/or will have CSF orexin levels of less than 110 pg/ml. Cataplexy are transient episodes of aberrant tone, most typically loss of tone, that can be associated with strong emotion. In pediatric onset narcolepsy, active motor phenomena are not uncommon. Cataplexy may be mistaken for syncope, tic disorder or seizures. Narcolepsy type 2 (NT2) does not have features of cataplexy and CSF orexin levels are normal. Sleep related hallucinations, also known as hypnogogic and hypnopompic are vivid hallucinations that can be auditory, visual or tactile and may occur independent of or in combination with an inability to move. 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 a histamine 3 (H3) receptor antagonist/inverse agonist (an antihistamine drug specific to that kind of receptors). It represents the first commercially available medication in its class, so that the US 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.
Dasotraline is a serotonin-norepinephrine-dopamine reuptake inhibitor (SNDRI) that was under development by Sunovion for the treatment of attention-deficit hyperactivity disorder (ADHD) and binge eating disorder (BED). Structurally, dasotraline is a stereoisomer of desmethylsertraline (DMS), which is an active metabolite of the marketed selective serotonin reuptake inhibitor (SSRI) antidepressant sertraline (Zoloft).
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.
Eugeroics, also known as wakefulness-promoting agents and wakefulness-promoting drugs, are a class of drugs that promote wakefulness and alertness. They are medically indicated for the treatment of certain sleep disorders including excessive daytime sleepiness (EDS) in narcolepsy or obstructive sleep apnea (OSA). Eugeroics are also often prescribed off-label for the treatment of EDS in idiopathic hypersomnia. In contrast to classical psychostimulants, such as methylphenidate and amphetamine, which are also used in the treatment of these disorders, eugeroics typically do not produce marked euphoria, and, consequently, have a lower addictive potential.
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 oral solution of calcium, magnesium, potassium, and sodium oxybates; in addition to several off-label treatments (primarily FDA-approved narcolepsy medications).