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.
Common of solriamfetol include headache, nausea, anxiety, and insomnia.
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 associated with
narcolepsy or obstructive sleep apnea in adults.
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.
Available forms
Solriamfetol is available in the form of 75 and 150mg oral tablets.
Side effects
of solriamfetol include
headache,
nausea, decreased appetite,
insomnia,
anxiety,
irritability,
feeling jittery,
dizziness,
chest discomfort, heart palpitations,
dry mouth,
hyperhidrosis,
abdominal pain,
constipation, and
diarrhea.
Misuse potential
Solriamfetol at higher-than-approved doses—specifically doses of 300, 600, and 1,200mg, which are 2 to 8 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).
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 and is a controlled substance in the
United States.
However, solriamfetol showed less misuse potential than Schedule II controlled stimulants like
amphetamine and
cocaine.
Consequently, the misuse potential of solriamfetol was rated as low and it was placed in the Schedule IV controlled substance category alongside phentermine.
Pharmacology
Pharmacodynamics
Solriamfetol is a norepinephrine–dopamine reuptake inhibitor (NDRI).
It binds to the dopamine transporter (DAT) and the norepinephrine transporter (NET) with affinities (K
i) of 14.2 μM and 3.7 μM, respectively.
It inhibits the reuptake of dopamine and norepinephrine with IC
50 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 (IC
50 > 100 μM).
In addition to its dopamine and norepinephrine reuptake inhibition, solriamfetol has been found to act as an
agonist of the human and rodent TAAR1 (EC
50 = 10–16μM) at clinically relevant concentrations similar to those of its DAT and NET inhibition.
Solriamfetol has no appreciable affinity for a variety of other targets, including the dopamine, serotonin, adrenergic,
GABA receptor, adenosine, histamine,
orexin receptor, benzodiazepine, and acetylcholine receptors.
Pharmacokinetics
The oral
bioavailability of solriamfetol is approximately 95%.
The median time to peak levels of solriamfetol is 2hours, with a range of 1.25 to 3.0hours.
A high-fat meal has minimal influence on the peak and total concentrations of solriamfetol, but does delay time to peak levels by approximately 1hour.
The apparent volume of distribution of solriamfetol is approximately 199L.
The plasma protein binding of solriamfetol is 13.3% to 19.4% over a concentration range of 0.059 to 10.1μg/mL.
Solriamfetol is minimally
metabolism in humans.
It shows
rate equation elimination with oral administration and has an elimination half-life of about 7.1hours.
The half-life of solriamfetol increases in the context of
renal impairment.
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.
Chemistry
Solriamfetol is a substituted phenethylamine derived from
phenylalanine and
phenylalaninol.
Its chemical name is (
R)-2-amino-3-phenylpropylcarbamate.
It is also known as
O-carbamoyl-
D-phenylalaninol.
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]
In 2019, solriamfetol was approved by the U.S. Food and Drug Administration (FDA) to improve wakefulness in adults with narcolepsy or obstructive sleep apnea.[ ][ ] It was granted orphan drug designation.[ ]
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,[ – Schedules of controlled substances] 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
Solriamfetol is under development for the treatment of attention deficit hyperactivity disorder (ADHD), binge eating disorder, and circadian rhythm sleep disorders.
