Characterization of the Neurochemical and Behavioral Effects of Solriamfetol (JZP-110), a Selective Dopamine and Norepinephrine Reuptake Inhibitor.
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Baladi MG, Forster MJ, Gatch MB, Mailman RB, Hyman DL, Carter LP, Janowsky A
Characterization of the Neurochemical and Behavioral Effects of Solriamfetol (JZP-110), a Selective Dopamine and Norepinephrine Reuptake Inhibitor.
J Pharmacol Exp Ther. 2018 Aug;366(2):367-376. doi: 10.1124/jpet.118.248120. Epub 2018 Jun 11.
- PubMed ID
- 29891587 [ View in PubMed]
- Abstract
Excessive sleepiness (ES) is associated with several sleep disorders, including narcolepsy and obstructive sleep apnea (OSA). A role for monoaminergic systems in treating these conditions is highlighted by the clinical use of US Food and Drug Administration-approved drugs that act on these systems, such as dextroamphetamine, methylphenidate, modafinil, and armodafinil. Solriamfetol (JZP-110) is a wake-promoting agent that is currently being evaluated to treat ES in patients with narcolepsy or OSA. Clinical and preclinical data suggest that the wake-promoting effects of solriamfetol differ from medications such as modafinil and amphetamine. The goal of the current studies was to characterize the mechanism of action of solriamfetol at monoamine transporters using in vitro and in vivo assays. Results indicate that solriamfetol has dual reuptake inhibition activity at dopamine (DA; IC50 = 2.9 muM) and norepinephrine (NE; IC50 = 4.4 muM) transporters, and this activity is associated in vivo with increased extracellular concentration of DA and NE as measured by microdialysis. Solriamfetol has negligible functional activity at the serotonin transporter (IC50 > 100 muM). Moreover, the wake-promoting effects of solriamfetol are probably owing to activity at DA and NE transporters rather than other neurotransmitter systems, such as histamine or orexin. The dual activity of solriamfetol at DA and NE transporters and the lack of significant monoamine-releasing properties of solriamfetol might explain the differences in the in vivo effects of solriamfetol compared with modafinil or amphetamine. Taken together, these data suggest that solriamfetol may offer an important advancement in the treatment of ES in patients with narcolepsy or OSA.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Solriamfetol Sodium-dependent dopamine transporter Protein Humans UnknownNot Available Details Solriamfetol Sodium-dependent noradrenaline transporter Protein Humans UnknownNot Available Details - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareMazindolSolriamfetol The risk or severity of adverse effects can be increased when Solriamfetol is combined with Mazindol. NomifensineSolriamfetol The risk or severity of adverse effects can be increased when Solriamfetol is combined with Nomifensine.