This is a list of investigational restless legs syndrome drugs, or drugs that are currently under development for clinical use for the treatment of restless legs syndrome (RLS) but are not yet approved.
Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses. The format of list items is "Name (Synonyms) – Mechanism of Action [Reference]".
This list was last comprehensively updated in September 2025. It is likely to become outdated with time.
Under development Phase 3 Ferric carboxymaltose (Ferinject; Injectafer; Iron-dextri-maltose; Iroprem; Renegy; VIT-45; Z-213) – iron replacement
Phase 2 BP-14979 (BP-1.4979) – dopamine D3 receptor partial agonist Ropinirole transdermal (Haruropi Tape; HP-3000) – dopamine D2-like receptor agonist
Preclinical ATH-399A (DWP-307399; HL-192) – nuclear receptor subfamily 4 group A member 2 (NR4A2) agonist
Not under development Suspended Aplindore (DAB-452; Palindore; SLS-006; WAY-DAB-452) – dopamine D2-like receptor agonist
No development reported NLS-2 (NLS2) – iron replacement Research programme: cannabinoid-based therapeutics - Axim Biotechnologies (Cannabidiol/Gabapentin; Cannbleph) – various actions
Discontinued Entacapone (Comtan; Comtess; OR-611) – catechol O-methyltransferase (COMT) inhibitor IPX-159 – undefined mechanism of action Istradefylline (KW-6002; Nourianz; Nouriast) – adenosine A2A receptor antagonist Pregabalin (CI-1008; isobutylgaba; Lyrica; PD-144723) – gabapentinoid (α2δ subunit-containing voltage-gated calcium channel ligand) Radafaxine (GW-353162; (2S,3S)-hydroxybupropion) – norepinephrine–dopamine reuptake inhibitor (NDRI) Research programme: dopamine receptor agonists - DarPharma (DAR-0300) – dopamine receptor agonist Safinamide (EMD-1195686; Equfina; FCE-26743; ME-2125; NW-1015; Onstryv; PNU-151774; Xadago; ZP-034) – monoamine oxidase MAO-B inhibitor and other actions
Clinically used drugs Approved drugs Gabapentin enacarbil (ASP-8825; GSK-1838262; Horizant; Regnite; Solzira; XP-13512) – gabapentinoid (α2δ subunit-containing voltage-gated calcium channel ligand) Oxycodone/naloxone (naloxone/oxycodone; Targin; Targinact; Targiniq) – combination of oxycodone (μ-opioid receptor agonist) and naloxone (orally inactive opioid receptor antagonist) (only in severe and treatment-refractory cases) Pramipexole (BI-Sifrol; Daquiran; Mirapex; Mirapexin; Pexola; Sifrol; SND-919) – dopamine D2-like receptor agonist Ropinirole (Adartrel; Repreve; Requip; Ropinirole IR) – dopamine D2-like receptor agonist Rotigotine transdermal (Leganto; N-0437; N-0923; Neupro; Nubrenza; SPM-962) – dopamine D2-like receptor agonist
Off-label drugs Benzodiazepines (GABAA receptor positive allosteric modulators) (e.g., clonazepam) Cannabinoids (cannabinoid receptor modulators) (e.g., cannabis, tetrahydrocannabinol (THC)) Dopamine precursors (indirect dopamine receptor agonists) (e.g., carbidopa/levodopa) Dopamine D2-like receptor agonists (e.g., cabergoline, pergolide) Gabapentinoids (α2δ subunit-containing voltage-gated calcium channel ligands) (e.g., gabapentin, pregabalin) Iron supplements (e.g., ferrous sulfate) Opioids (μ-opioid receptor agonists) (e.g., tramadol, codeine, morphine, oxycodone, hydrocodone, methadone, buprenorphine) (only in severe and treatment-refractory cases) Others (e.g., amantadine, baclofen, bupropion, carbamazepine, clonidine, corticosteroids, dipyridamole, ketamine, lamotrigine, levetiracetam, orphenadrine, oxcarbazepine, perampanel, physostigmine, rasagiline, rifaximin, selegiline, topiramate, valproic acid)
See also List of investigational drugs List of investigational Parkinson's disease drugs
References
External links AdisInsight - Springer