 Molecular structure of solriamfetol | |
 3D representation of a solriamfetol molecule | |
| 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;O-Carbamoyl-D-phenylalaninol |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a619040 |
| License data | |
| Routes of administration | By mouth[1] |
| Drug class | Norepinephrine–dopamine reuptake inhibitor;Wakefulness-promoting agent |
| ATC code | |
| Legal status | |
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| Pharmacokinetic data | |
| Bioavailability | ~95%[1] |
| Protein binding | 13.3–19.4%[1] |
| Metabolism | Minimal (~1%)[1] |
| Metabolites | •N-Acetylsolriamfetol (~1%)[1] |
| Eliminationhalf-life | ~7.1 hours[1] |
| Excretion | Urine (95% unchanged) |
| Identifiers | |
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| CAS Number | |
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| IUPHAR/BPS | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
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| CompTox Dashboard(EPA) | |
| 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 nameSunosi, is awakefulness-promoting medication used in the treatment ofexcessive sleepiness related tonarcolepsy andsleep apnea.[1][5][6] It is takenby mouth.[1]
Commonside effects of solriamfetol includeheadache,nausea,anxiety, andtrouble sleeping.[1] It is anorepinephrine–dopamine reuptake inhibitor (NDRI) and is thought to work by increasing levels of theneurotransmittersnorepinephrine anddopamine in thebrain.[1][5] Solriamfetol has also been found to act as aTAAR1agonist, an action that may also be involved in its effects.[7]
The drug was discovered by a subsidiary ofSK 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 ofattention deficit hyperactivity disorder (ADHD),binge eating disorder, andcircadian rhythm sleep disorders.[9]
Solriamfetol is used to promotewakefulness in the treatment ofexcessive daytime sleepiness associated withnarcolepsy orobstructive sleep apnea in adults.[1] It appears to be more effective in improving excessive daytime sleepiness associated with obstructive sleep apnea than certain otherwakefulness-promoting agents includingmodafinil,armodafinil, andpitolisant.[10]
Solriamfetol is available in the form of 75 and 150 mgoraltablets.[1]
Side effects of solriamfetol includeheadache,nausea,decreased appetite,insomnia,anxiety,irritability,feeling jittery,dizziness,chest discomfort,heart palpitations,dry mouth,increased sweating,abdominal pain,constipation, anddiarrhea.[1]
Solriamfetol at higher-than-approved doses—specifically doses of 300, 600, and 1,200 mg, which are 2 to 8 times the maximum recommended dose—producesdrug-liking responses, includingelevated mood andfeelings of relaxation, that are similar in degree to those ofphentermine (aSchedule IVcontrolled substance).[1] Elevated mood occurred in 2.4% withplacebo, 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 significantmisuse potential and is acontrolled substance in theUnited States.[1] However, solriamfetol showed less misuse potential thanSchedule II controlled stimulants likeamphetamine andcocaine.[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]
Solriamfetol is anorepinephrine–dopamine reuptake inhibitor (NDRI).[1] It binds to thedopamine transporter (DAT) and thenorepinephrine transporter (NET) withaffinities (Ki) of 14.2 μM and 3.7 μM, respectively.[1] It inhibits the reuptake of dopamine and norepinephrine withIC50 values of 2.9 μM and 4.4 μM, respectively.[1] It has weak affinity for theserotonin 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 anagonist of the human and rodentTAAR1 (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 thedopamine,serotonin,adrenergic,GABA,adenosine,histamine,orexin,benzodiazepine, andacetylcholine receptors.[1]
Theoralbioavailability of solriamfetol is approximately 95%.[1] The mediantime 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 apparentvolume of distribution of solriamfetol is approximately 199 L.[1] Theplasma 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 minimallymetabolized in humans.[1] It showsfirst-orderelimination with oral administration and has anelimination half-life of about 7.1 hours.[1] The half-life of solriamfetol increases in the context ofrenal impairment.[1] Approximately 95% of a dose of solriamfetol is eliminated inurine as unchanged solriamfetol and 1% or less is eliminated as the minor inactivemetaboliteN-acetylsolriamfetol.[1]
Solriamfetol is asubstituted phenethylamine derived fromd-phenylalanine andD-phenylalaninol.[12] Its chemical name is (R)-2-amino-3-phenylpropylcarbamate.[13][12] It is also known asO-carbamoyl-D-phenylalaninol.[13]
The drug was discovered by a subsidiary ofSK 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 agreed to pay Aerial and SK up to $272 million in milestone payments, as well as double-digit royalties to SK.[8][15]
In 2019, solriamfetol was approved by the U.S.Food and Drug Administration (FDA) to improve wakefulness in adults withnarcolepsy orobstructive sleep apnea.[16][17] It was grantedorphan drug designation.[18]
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]
During development it has been called SKL-N05, ADX-N05, ARL-N05, and JZP-110.[9]
In the United States, solriamfetol is aSchedule 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 theEuropean Union, a prescription is required.[4]
Solriamfetol is under development for the treatment ofattention deficit hyperactivity disorder (ADHD),binge eating disorder, andcircadian rhythm sleep disorders.[9][22] As of September 2023, it is inphase 3clinical trials for ADHD andphase 2 clinical trials for binge eating disorder and circadian rhythm sleep disorders.[9][22] Acase report of solriamfetol for the treatment of ADHD has been published.[23] Solriamfetol was also under development for the treatment ofdepressive disorders, but development for this indication was discontinued.[9] In May 2024, theNational Institutes of Health (NIH) announced a trial of solriamfetol for the treatment oflong COVID.[24] In September 2025, a small double-blind, placebo-controlled study found positive results in "improving fatigue and executive functioning in patients with ME/CFS."[25]
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.
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