• Source: List of investigational attention deficit hyperactivity disorder drugs

    • This is a list of investigational attention deficit hyperactivity disorder drugs, or drugs that are currently under development for clinical use in the treatment of attention deficit hyperactivity disorder (ADHD) but are not yet approved.
    Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses.
    This list was last comprehensively updated in September 2021. It is likely to become outdated with time.


    Under development




    = Preregistration

    =
    ATT-377 – Combination treatment of Methylphenidate ER, cyproheptadine
    TRN-110 [extended-release] – undefined mechanism / extended-release form of an undisclosed drug


    = Phase 3 clinical trials

    =
    Centanafadine [sustained-release] (centanafadine SR, CTN-SR, EB-1020, EB-1020 SR) – serotonin–norepinephrine–dopamine reuptake inhibitor
    Dexmethylphenidate [controlled release] (CTX-1301) – norepinephrine–dopamine reuptake inhibitor
    Edivoxetine (LY-2216684) – norepinephrine reuptake inhibitor
    Molindone [extended-release] (AFX-2201, EN-1733A, molindone XR, SPN-810, SPN-810M, Zalvari) – antipsychotic / dopamine D2 receptor antagonist and serotonin receptor modulator (e.g., serotonin 5-HT2B and 5-HT2A receptor antagonist) — specifically under development for impulsive aggression in ADHD
    Serdexmethylphenidate (KP-484) – dexmethylphenidate prodrug / norepinephrine–dopamine reuptake inhibitor
    Solriamfetol (ADX-N05, ARL-N05, JZP-110, SKL-N05; Sunosi) – norepinephrine–dopamine reuptake inhibitor


    = Phase 2 clinical trials

    =
    CX-717 – ampakine / AMPA receptor modulator
    Mazindol [controlled release] (NLS-0, NLS-1, NLS-10, NLS-13, NLS-2, Nolazol, Quilience) – serotonin–norepinephrine–dopamine reuptake inhibitor
    PDC-1421 (BLI-1005) – norepinephrine reuptake inhibitor


    = Phase 1 clinical trials

    =
    AFX-2401 – "neurotransmitter modulator"
    Atomoxetine [oral solution] (TAH-9922) – norepinephrine reuptake inhibitor
    Dextroamphetamine [abuse-deterrent immediate-release] (ADAIR) – norepinephrine–dopamine releasing agent


    = Preclinical/research

    =
    Atomoxetine [oral suspension] – norepinephrine reuptake inhibitor
    Dextroamphetamine [controlled release] (CTX-1302) – norepinephrine–dopamine releasing agent
    NNI-351 – DYRK1A inhibitor and "neurogenesis enhancer"


    No development reported


    AFI-002 – undefined mechanism
    Altropane (123-I Altropane®, [123I]-E-IACFT Injection, [123I]NAV5001, CFT, Iodine-123-E-IACFT Injection, NAV-5001, O-587) – dopamine reuptake inhibitor / single-photon emission-computed tomography enhancer
    Amphetamine [oral abuse-deterrent immediate-release] (ADAIR) – norepinephrine–dopamine releasing agent
    Bavisant (BEN-2001, JNJ-1074, JNJ-31001074) – histamine H3 receptor antagonist
    BCWP-E003 – undefined mechanism
    BLI-1008 – undefined mechanism
    Brilaroxazine (RP-5000, RP-5063) – atypical antipsychotic / dopamine receptor partial agonist and serotonin receptor modulator
    Cannabidiol/gabapentin (Cannbleph) – cannabinoid receptor modulator and gabapentinoid
    Ciforadenant (CPI-444, V-81444) – adenosine A2A receptor antagonist
    CM-4612 (CM-ADHD, CM-AT, CM-PK) – gastrointestinal/pancreatic enzyme replacement therapy
    CRD-102 – undefined mechanism
    Dasotraline (DSP-225289, SEP-225289, SEP-0225289, SEP-225289-HCI, SEP-289) – serotonin–norepinephrine–dopamine reuptake inhibitor
    Dextroamphetamine [abuse-resistant] (PF-08, PFR 08001, PFR08026) – norepinephrine–dopamine releasing agent
    Dextroamphetamine sulfate [modified release capsules] (HLD-900, HLD-100) – norepinephrine–dopamine releasing agent
    Dopamine [intranasal] (DopaMat, MPP-18) – dopamine receptor agonist
    Eltoprazine (DU-28853) – serotonin 5-HT1A and 5-HT1B receptor agonist
    Fasoracetam [co-crystallised] (AEVI-004, NFC-1) – racetam / metabotropic glutamate receptor modulator
    GTS-21 (DMXB-A, DMXB-A sustained release, DMXB-A-SR) – α7 nicotinic acetylcholine receptor agonist
    Guanfacine [once-daily] (Guanfacine Carrier Wave, SPD-547) – α2-adrenergic receptor agonist
    IPX-233 (IPX233 ER C0003, IPX233-C0001, IPX233-C0002, IPX233-T0001, IPX233-T0002) – central nervous system stimulant
    Masupirdine (M1, M1 of SUVN-502, SUVN-502, SVN-502) – serotonin 5-HT6 receptor antagonist
    Methylphenidate [extended-release/abuse-resistant] (COL-171) – norepinephrine–dopamine reuptake inhibitor
    Methylphenidate [fast dissolve tablet] [Samyang Holdings Biopharmaceuticals] – norepinephrine–dopamine reuptake inhibitor
    Methylphenidate [transdermal system] (SHX-009) – norepinephrine–dopamine reuptake inhibitor
    Methylphenidate/naltrexone (AVK-001) – norepinephrine–dopamine reuptake inhibitor and opioid receptor antagonist
    Nic-12 – undefined mechanism
    NLS-2 – antianaemic / heavy metal / iron replacement
    PD-3044 – dopamine reuptake inhibitor
    Pitolisant (tiprolisant; BF-2.649, BF-2649, Ozawade, Wakix) – histamine H3 receptor antagonist
    R-Sibutramine metabolite ((+)-desmethylsibutramine, (+)-didesmethylsibutramine, R-DDMS, R-desmethylsibutramine, R-didesmethylsibutramine) – serotonin–norepinephrine–dopamine reuptake inhibitor
    Selegiline [transdermal] (Emsam) – monoamine oxidase B inhibitor
    SKL-13865 (SKL-ADHD) – norepinephrine–dopamine reuptake inhibitor
    Sofinicline (A-422894.0, ABT-894) – α4β2 nicotinic acetylcholine receptor modulator
    SPN-811 – undefined mechanism
    Taminadenant (NIR-178, PBF-509) – adenosine A2A receptor antagonist


    = Research programmes

    =
    Ampakines / AMPA receptor modulators [RespireRx] (CX-516, CX-614, CX-707, CX-929, CX-1501, CX-1763, CX-1796, CX-1837, CX-1846, CX-1942, CX-2007, CX-2076)
    Cannabis extracts [Cannabis Science] (CBIS GAP-001, CBIS LC-001, CBIS OBLD-001, CBIS OCD-001, CBIS PC-001, CBIS PPC-001, CBIS PS-001, CBIS SD-001, CBIS SSA-001, CBIS-OS-001, CBIS-PTSD-001, CS NEURO 1, CS-S/BCC-1, CS-TATI-1) – cannabinoid receptor modulators
    Norepinephrine reuptake inhibitors / adrenergic receptor antagonists [Pfizer] (NRI-022, NRI-193, WAY-253203, WAY-256805, WAY-260022, WAY-315193, WAY-318068)
    Pim2 / PolyPhetamine [ITL Pharma]
    Subtype-selective glutamate NMDA receptor modulators / glutamate NR2B receptor modulators [Novartis]


    Not under development




    = Development discontinued

    =
    ABT-418 – nicotinic acetylcholine receptor agonist
    Amphetamine [transdermal patch] [Noven/Takeda] – norepinephrine–dopamine releasing agent
    Ampreloxetine (TD-9855) – norepinephrine reuptake inhibitor
    AR-08 – adrenergic receptor agonist
    Aripiprazole (Abilify, Abilify Maintena, Abilify MyCite, Abilitat, Ao Pai, Aripiprazole depot, Aripiprazole ECER tablets, Arlemide; OPC-14597, OPC-14597 IMD, OPC-31) – atypical antipsychotic / dopamine receptor partial agonist and serotonin receptor modulator
    AZD-5213 – histamine H3 receptor antagonist
    Bifemelane (SON-216) – monoamine oxidase inhibitor and weak norepinephrine reuptake inhibitor
    Bradanicline (ATA-101, TC-0569, TC-5619, TC-5619-238) – α7 nicotinic acetylcholine receptor agonist
    Brexpiprazole (Rexulti, Rxulti; Lu-AF41156, OPC-34712, OPDC-34712) – atypical antipsychotic / dopamine receptor partial agonist and serotonin receptor modulator
    Buspirone [transdermal] (BuSpar Patch) – serotonin 5-HT1A receptor partial agonist, other actions
    Cipralisant (GT-2331; Perceptin) – histamine H3 receptor antagonist
    CX-516 (1-BCP, AMPAlex, BDP-12, SPD-420) – ampakine / AMPA receptor modulator
    CX-1739 – ampakine / AMPA receptor modulator
    Donepezil (Aricept, Aricept D, Aricept Dry Syrup, Aricept Evess, Aricept ODT, Aricept SR, Donepezil SR, E-2020, E-2022, Eranz) – acetylcholinesterase inhibitor
    Droxidopa (3,4-dihydroxyphenylserine, 3,4-threo-DOPS, L-threo-dihydroxyphenylserine, L-threodops, Northera, threo-dopaserine, threo-DOPS) – prodrug of norepinephrine / adrenergic receptor agonist
    Fasoracetam (AEVI-001, LAM-105, MDGN-001, NFC-1, NS-105) – racetam / metabotropic glutamate receptor modulator
    Ispronicline (AZD-3480, RJR-1734, TC 01734, TC-1734, TC-1734-112) – α4β2-nicotinic acetylcholine receptor agonist
    KP-106 (dextroamphetamine prodrug oral film) – norepinephrine–dopamine releasing agent
    Lauflumide (flmodafinil, bisfluoromodafinil; NLS-14, NLS-4) – weak dopamine reuptake inhibitor, possibly other actions
    Manifaxine (BW-1555U88, GW-320659) – norepinephrine–dopamine reuptake inhibitor
    Mecamylamine (Inversine, Tridmac) – nicotinic acetylcholine receptor antagonist
    MEM-68626 – 5-HT6 receptor antagonist
    Metadoxine [sustained/extended-release] (pyridoxine-pyrrolidone carboxylate, pyridoxine pidolate; MDX, metadoxine SR, MG-01CI) – serotonin 5-HT2B receptor antagonist, GABA modulator, other actions
    Methylphenidate [transdermal patch] (TAH-9901) – norepinephrine–dopamine reuptake inhibitor
    MK-0249 – histamine H3 receptor antagonist
    Modafinil (AFT-801, Alertec, Attenace, CN-801, CRL-40476, Modasamil, Modasonil, Modavigil, Modiodal, Provigil, Sparlon, Vigil) – weak dopamine reuptake inhibitor, possibly other actions
    Nicotine/opipramol (ND-0801; opipramol/nicotine) – tricyclic antidepressant / monoamine and sigma receptor modulator and nicotinic acetylcholine receptor agonist
    NLS-8 – (melafenoxate) undefined mechanism
    NS-2359 (GSK-372475) – serotonin–norepinephrine–dopamine reuptake inhibitor
    OPC-64005 – serotonin–norepinephrine–dopamine reuptake inhibitor
    ORG-26576 (ORG26576) – ampakine / AMPA receptor modulator
    PF-3654746 (PF-03654746) – histamine H3 receptor antagonist
    Phacetoperane (NLS-3) – methylphenidate analogue / central nervous system stimulant / norepinephrine–dopamine reuptake inhibitor (?)
    Pirepemat (IRL-752) – "cortical enhancer" / serotonin 5-HT7 receptor antagonist and α2C-adrenergic receptor antagonist, other actions
    Pozanicline (A-87089.0, ABT-089) – α4β2 nicotinic acetylcholine receptor agonist
    SEP-225432 – serotonin–norepinephrine–dopamine reuptake inhibitor
    SGS-742 (CGP-36742, DVD-742, Lu-AE58479, SGS-742) – GABAB receptor antagonist
    SPD-483 – undefined mechanism
    SPD-554 (Guanfacine Carrier Wave project) – α2-adrenergic receptor agonist
    SPI-339 (NEO-339) – undefined mechanism
    TAK-137 – AMPA receptor potentiator
    TC-6683 (AZD 1446, TC-6683) – α4β2 nicotinic acetylcholine receptor agonist
    Tipepidine [sustained-release] (TS-141) – GIRK inhibitor
    Vortioxetine (Brintellix, LU-AA21004, LuAA 21004, Trintellix) – antidepressant / serotonin reuptake inhibitor and serotonin receptor modulator


    Research programmes


    Potassium channel modulators [Astellas Pharma/Icagen]


    = Formal development never or not yet started

    =
    Dopamine precursors (L-phenylalanine, L-tyrosine, L-DOPA (levodopa))


    Clinically used drugs




    = Approved drugs

    =


    Norepinephrine–dopamine releasing agents


    Amphetamine (Adzenys ER, Adzenys XR-ODT, Dyanavel XR, Evekeo, Evekeo ODT)
    Dextroamphetamine (Dexedrine, Zenzedi, Xelstrym)
    Fenethylline (Biocapton, Captagon, Fitton) – amphetamine and theophylline prodrug — discontinued/no longer used
    Levoamphetamine (Cydril) – discontinued/no longer used
    Lisdexamfetamine (Elvanse, Tyvense, Venvanse, Vyvanse) – dextroamphetamine prodrug
    Methamphetamine (dextromethamphetamine; Desoxyn, Methampex)
    Mixed amphetamine salts (Adderall, Adderall XR, Mydayis)
    Pemoline (Betanamin, Ceractiv, Cylert, Tradon) – withdrawn/discontinued due to toxicity


    Norepinephrine–dopamine reuptake inhibitors


    Dexmethylphenidate (Focalin, Focalin XR)
    Methylphenidate (Adhansia XR, Aptensio XR, Benjorna, Biphentin, Concerta, Cotempla XR-ODT, Daytrana, Equasym, Foquest, Jornay PM, Metadate, Metadate CD, Metadate ER, Methydur, MethyPatch, Oradur, QuilliChew ER, Quillivant XR, Ritalin, Ritalin SR)
    Serdexmethylphenidate/dexmethylphenidate (Azstarys)


    Norepinephrine reuptake inhibitors


    Atomoxetine (tomoxetine; Strattera)
    Viloxazine [extended-release] (Qelbree)


    α2-Adrenergic receptor agonists


    Clonidine (Catapres, CloniBID, Clonicel, Jenloga XR, Kapvay)
    Guanfacine (Connexyn, Intuniv, Intuniv XR, Tenex)


    = Off-label drugs

    =
    Bupropion (Wellbutrin) – norepinephrine–dopamine reuptake inhibitor and nicotinic acetylcholine receptor antagonist
    Modafinil (Provigil) – weak dopamine reuptake inhibitor, possibly other actions
    Reboxetine (Edronax) – norepinephrine reuptake inhibitor
    Serotonin–norepinephrine reuptake inhibitors (e.g., venlafaxine (Effexor), duloxetine (Cymbalta))
    Tricyclic antidepressants (e.g., desipramine (Norpramin) – norepinephrine reuptake inhibitor)


    See also


    List of investigational drugs


    References




    Further reading


    Childress A, Tran C (2016). "Current Investigational Drugs for the Treatment of Attention-Deficit/Hyperactivity Disorder". Expert Opin Investig Drugs. 25 (4): 463–74. doi:10.1517/13543784.2016.1147558. PMID 26814173. S2CID 207477710.
    Jain R, Katic A (August 2016). "Current and Investigational Medication Delivery Systems for Treating Attention-Deficit/Hyperactivity Disorder". Prim Care Companion CNS Disord. 18 (4). doi:10.4088/PCC.16r01979. PMID 27828696.
    Buoli M, Serati M, Cahn W (2016). "Alternative pharmacological strategies for adult ADHD treatment: a systematic review". Expert Rev Neurother. 16 (2): 131–44. doi:10.1586/14737175.2016.1135735. PMID 26693882. S2CID 33004517.
    Nageye F, Cortese S (July 2019). "Beyond stimulants: a systematic review of randomised controlled trials assessing novel compounds for ADHD". Expert Rev Neurother. 19 (7): 707–717. doi:10.1080/14737175.2019.1628640. PMID 31167583. S2CID 174810839.
    Perugi G, Pallucchini A, Rizzato S, Pinzone V, De Rossi P (August 2019). "Current and emerging pharmacotherapy for the treatment of adult attention deficit hyperactivity disorder (ADHD)". Expert Opin Pharmacother. 20 (12): 1457–1470. doi:10.1080/14656566.2019.1618270. PMID 31112441. S2CID 162170434.
    Childress AC, Beltran N, Supnet C, Weiss MD (March 2021). "Reviewing the role of emerging therapies in the ADHD armamentarium". Expert Opin Emerg Drugs. 26 (1): 1–16. doi:10.1080/14728214.2020.1846718. PMID 33143485. S2CID 226251694.


    External links


    AdisInsight - Springer

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