Solriamfetol, sold under the brand name Sunosi, is a

wakefulness-promoting Eugeroics (originally "eugrégorique" or "eugregoric"), 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 cer ...

medication used in the treatment of excessive sleepiness related to

narcolepsy Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affect ...

and

sleep apnea Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of shallow breathing during sleep occur more often than normal. Each pause can last for a few seconds to a few minutes and they happen many tim ...

. It is taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

. Common

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s of solriamfetol include headache,

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

, and

trouble sleeping Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

. It is a norepinephrine–dopamine reuptake inhibitor (NDRI) and is thought to work by increasing levels of the neurotransmitters

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad' ...

and dopamine in the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...

. The drug was discovered by a subsidiary of

SK Group SK Group ( Korean: SK그룹, 에스케이그룹) is the second largest South Korean chaebol behind Samsung Group. SK Group is composed of 186 subsidiaries and affiliates that share the SK brand name and the group's management culture, named SKMS ...

, which licensed rights outside of eleven countries in Asia to Aerial Pharma in 2011.

Medical uses

Solriamfetol is used to promote

wakefulness Wakefulness is a daily recurring brain state and state of consciousness in which an individual is conscious and engages in coherent cognitive and behavioral responses to the external world. Being awake is the opposite of being asleep, in which m ...

in the treatment of

excessive daytime sleepiness 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 encompass ...

associated with

or obstructive sleep apnea in adults.

Available forms

Solriamfetol is available in the form of 75 and 150mg

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or or ...

tablets.

Side effects

Side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s of solriamfetol include headache,

decreased appetite Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others ...

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

irritability Irritability (also called as crankiness) is the excitatory ability that living organisms have to respond to changes in their environment. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessi ...

feeling jittery Psychomotor agitation is a symptom in various disorders and health conditions. It is characterized by unintentional and purposeless motions and restlessness, often but not always accompanied by emotional distress. Typical manifestations include ...

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...

chest discomfort Chest pain is pain or discomfort in the chest, typically the front of the chest. It may be described as sharp, dull, pressure, heaviness or squeezing. Associated symptoms may include pain in the shoulder, arm, upper abdomen, or jaw, along with ...

heart palpitation Palpitations are perceived abnormalities of the heartbeat characterized by awareness of cardiac muscle contractions in the chest, which is further characterized by the hard, fast and/or irregular beatings of the heart. Symptoms include a rap ...

dry mouth Xerostomia, also known as dry mouth, is dryness in the mouth, which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause. This symptom is very common and is often seen as a side eff ...

, increased sweating,

abdominal pain Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Common causes of pain in the abdomen include gastroenteritis and irritable bowel syndrome. About 15% of people have a m ...

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...

, and

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

. Solriamfetol at higher-than-approved doses (300, 600, and 1,200mg—two to four times the maximum recommended dose) produces drug-liking responses, including elevated mood and feelings of relaxation, similar in degree to those of

phentermine Phentermine ( phenyl- tertiary-butyl amine), with several brand names including Ionamin and Sentis, is a medication used together with diet and exercise to treat obesity. It is taken by mouth for up to a few weeks at a time, after which the ben ...

. Elevated mood occurred in 2.4% with

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. In general, placebos can af ...

, 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. As such, solriamfetol has significant misuse potential and is a

controlled substance A controlled substance is generally a drug or chemical whose manufacture, possession and use is regulated by a government, such as illicitly used drugs or prescription medications that are designated by law. Some treaties, notably the Single ...

in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...

Pharmacology

Pharmacodynamics

Solriamfetol is a norepinephrine–dopamine reuptake inhibitor (NDRI). It binds to the

dopamine transporter The dopamine transporter (also dopamine active transporter, DAT, SLC6A3) is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synaptic cleft back into cytosol. In the cytosol, other transporters sequester the dop ...

and the

norepinephrine transporter The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene. NET is a monoamine transporter and is responsible for the sodium- ...

with affinities (K_i) of 14.2 μM and 3.7 μM, respectively). It inhibits the reuptake of dopamine and norepinephrine with IC₅₀ values of 2.9 μM and 4.4 μM, respectively. It has weak affinity for the

serotonin transporter The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein tha ...

(K_i = 81.5 μM) and does not appreciably inhibit serotonin reuptake (IC₅₀ > 100 μM). Solriamfetol has no appreciable affinity for a variety of other targets, including the dopamine, serotonin,

adrenergic Adrenergic means "working on adrenaline (epinephrine) or noradrenaline (norepinephrine)" (or on their receptors). When not further qualified, it is usually used in the sense of enhancing or mimicking the effects of epinephrine and norepinephrine ...

, GABA, adenosine,

histamine Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discovered ...

orexin Orexin (), also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. The most common form of narcolepsy, type 1, in which the individual experiences brief losses of muscle tone ("drop attacks" or cataplexy) ...

, benzodiazepine, and

acetylcholine receptor An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter. Classification Like other transmembrane receptors, acetylcholine receptors are classified according ...

Pharmacokinetics

The time to peak levels of solriamfetol is about 2hours (range 1.25–3.0hours). Solriamfetol is minimally

metabolized Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

in humans. Its

elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

is about 7.1hours.

Chemistry

Solriamfetol is derived from d- phenylalanine and its chemical name is (''R'')-2-amino-3-phenylpropylcarbamate.

History

The drug was discovered by a subsidiary of

, which licensed rights outside of eleven countries in Asia to Aerial Pharma in 2011. Aerial ran two Phase II trials of the drug in narcolepsy before selling the license to solriamfetol to Jazz in 2014;

Jazz Pharmaceuticals Jazz Pharmaceuticals plc (a merger of Jazz Pharmaceuticals, Inc. and Azur Pharma plc) is a biopharmaceutical company based in Ireland. It was founded in 2003. One of the company's considerable products is the United States Food and Drug Admini ...

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. In 2019, solriamfetol was approved in the United States to improve wakefulness in adults with narcolepsy or obstructive sleep apnea (OSA). It was granted orphan drug designation. The U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(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). The trials were conducted in Canada, Europe, and the United States. Solriamfetol was approved for medical use in the European Union in January 2020. 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.

Society and culture

Names

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

Legal status

In the United States, solriamfetol is a Schedule IV controlled substance, meaning that it has an accepted medical use and a low potential for abuse, but that abuse may lead to physical or psychological dependence. A prescription is required, and can only be refilled up to five times in a six-month period. Retrieved 2014-01-07 In countries of the

European Union The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been de ...

, a prescription is required.

Research

Attention deficit hyperactivity disorder

case report In medicine, a case report is a detailed report of the symptoms, signs, diagnosis, treatment, and follow-up of an individual patient. Case reports may contain a demographic profile of the patient, but usually describe an unusual or novel occurrenc ...

of solriamfetol for the treatment of

attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...

(ADHD) exists.

References

External links

* * {{Portal bar , Medicine Carbamates Norepinephrine–dopamine reuptake inhibitors Orphan drugs Phenethylamines Stimulants