Solriamfetol

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. It is taken by mouth.

Common side effects of solriamfetol include headache, nausea, anxiety, and trouble sleeping. 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. Solriamfetol has also been found to act as a TAAR1 agonist, an action that may also be involved in its effects.

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

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.

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

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.

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—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.

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 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). In addition to its dopamine and norepinephrine reuptake inhibition, solriamfetol has been found to act as an agonist of the human and rodent TAAR1 (EC₅₀ = 10–16 μM) 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, adenosine, histamine, orexin, benzodiazepine, and acetylcholine receptors.