Solriamfetol, sold under the brand name Sunosi, is a wakefulness-promoting medication used in the treatment of

excessive 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 ...

related to narcolepsy and sleep apnea. It is taken by mouth. Common side effects of solriamfetol include

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

, nausea, anxiety, 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

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

s norepinephrine and

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

in the brain. The drug was discovered by a subsidiary of SK Group, which licensed rights outside of eleven countries in Asia to Aerial Pharma in 2011.

Medical uses

Solriamfetol is used to promote wakefulness 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 narcolepsy or

obstructive sleep apnea Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder and is characterized by recurrent episodes of complete or partial obstruction of the upper airway leading to reduced or absent breathing during sleep. These episod ...

in adults.

Available forms

Solriamfetol is available in the form of 75 and 150mg oral

tablet Tablet may refer to: Medicine * Tablet (pharmacy), a mixture of pharmacological substances pressed into a small cake or bar, colloquially called a "pill" Computing * Tablet computer, a mobile computer that is primarily operated by touching the s ...

Side effects

Side effects of solriamfetol include

, nausea, decreased appetite, insomnia, anxiety, irritability, feeling jittery, dizziness, chest discomfort, heart palpitations, dry mouth, increased sweating, abdominal pain, constipation, and diarrhea. Solriamfetol at higher-than-approved doses (300, 600, and 1,200mg—two to four times the maximum recommended dose) produces

drug-liking Drug liking is a measure of the pleasurable (hedonic) experience when a person consumes drugs. It is commonly used to study the misuse liability of drugs. Drug liking is often measured using unipolar and bipolar visual analogue scales (VAS), such ...

responses, including

elevated mood Euphoria ( ) is the experience (or affect (psychology), affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or ma ...

and

feelings of relaxation Relaxation in psychology is the emotional state of a living being, of low tension, in which there is an absence of arousal, particularly from negative sources such as anger, anxiety, or fear. According to Oxford Dictionaries (website), Oxford Dic ...

, similar in degree to those of phentermine. 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. As such, solriamfetol has significant

misuse potential Substance abuse, also known as drug abuse, is the use of a drug in amounts or by methods which are harmful to the individual or others. It is a form of substance-related disorder. Differing definitions of drug abuse are used in public health, ...

and is a controlled substance in the United States.

Pharmacology

Pharmacodynamics

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

affinities In post-classical history, an affinity was a collective name for the group ( retinue) of (usually) men whom a lord gathered around himself in his service; it has been described by one modern historian as "the servants, retainers, and other foll ...

(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 (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

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

, adrenergic, GABA,

adenosine Adenosine ( symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside building ...

, histamine, orexin,

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

, and acetylcholine receptors.

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 is about 7.1hours.

Chemistry

Solriamfetol is derived from d-

phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...

and its chemical name is (''R'')-2-amino-3-phenylpropylcarbamate.

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. Aerial ran two Phase II trials of the drug in narcolepsy 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. 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 An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases. The assignment of ...

designation. 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). 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 The prohibition of drugs through sumptuary legislation or religious law is a common means of attempting to prevent the recreational use of certain intoxicating substances. While some drugs are illegal to possess, many governments regulate the ...

, 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, 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 occurrence ...

of solriamfetol for the treatment of attention deficit hyperactivity disorder (ADHD) exists.

References

External links

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