List of investigational attention deficit hyperactivity disorder drugs

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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.

Under development

Preregistration

  • TRN-110 [extended-release] – undefined mechanism / extended-release form of an undisclosed drug [1]

Phase 3 clinical trials

  • Centanafadine [sustained-release] (centanafadine SR, CTN-SR, EB-1020, EB-1020 SR) – serotonin–norepinephrine–dopamine reuptake inhibitor [2]
  • Dexmethylphenidate [controlled release] (CTX-1301) – norepinephrine–dopamine reuptake inhibitor [3]
  • Edivoxetine (LY-2216684) – norepinephrine reuptake inhibitor [4]
  • 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 [5][1][2]
  • Serdexmethylphenidate (KP-484) – dexmethylphenidate prodrug / norepinephrine–dopamine reuptake inhibitor [6] [7]
  • Solriamfetol (ADX-N05, ARL-N05, JZP-110, SKL-N05; Sunosi) – norepinephrine–dopamine reuptake inhibitor [8]

Phase 2 clinical trials

  • CX-717 – ampakine / AMPA receptor modulator [9]
  • Mazindol [controlled release] (NLS-0, NLS-1, NLS-10, NLS-13, NLS-2, Nolazol, Quilience) – serotonin–norepinephrine–dopamine reuptake inhibitor [10]
  • PDC-1421 (BLI-1005) – norepinephrine reuptake inhibitor [11]

Phase 1 clinical trials

  • AFX-2401 – "neurotransmitter modulator" [12]
  • Atomoxetine [oral solution] (TAH-9922) – norepinephrine reuptake inhibitor [13]
  • Dextroamphetamine [abuse-deterrent immediate-release] (ADAIR) – norepinephrine–dopamine releasing agent [14]

Preclinical/research

  • Atomoxetine [oral suspension] – norepinephrine reuptake inhibitor [15]
  • Dextroamphetamine [controlled release] (CTX-1302) – norepinephrine–dopamine releasing agent [16]
  • NNI-351 – DYRK1A inhibitor and "neurogenesis enhancer" [17]

No development reported

  • AFI-002 – undefined mechanism [18]
  • 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 [19]
  • Amphetamine [oral abuse-deterrent immediate-release] (ADAIR) – norepinephrine–dopamine releasing agent [20]
  • Bavisant (BEN-2001, JNJ-1074, JNJ-31001074) – histamine H3 receptor antagonist [21]
  • BCWP-E003 – undefined mechanism [22]
  • BLI-1008 – undefined mechanism [23]
  • Brilaroxazine (RP-5000, RP-5063) – atypical antipsychotic / dopamine receptor partial agonist and serotonin receptor modulator [24]
  • Cannabidiol/gabapentin (Cannbleph) – cannabinoid receptor modulator and gabapentinoid [25]
  • Ciforadenant (CPI-444, V-81444) – adenosine A2A receptor antagonist [26]
  • CM-4612 (CM-ADHD, CM-AT, CM-PK) – gastrointestinal/pancreatic enzyme replacement therapy [27]
  • CRD-102 – undefined mechanism [28]
  • Dasotraline (DSP-225289, SEP-225289, SEP-0225289, SEP-225289-HCI, SEP-289) – serotonin–norepinephrine–dopamine reuptake inhibitor [29]
  • Dextroamphetamine [abuse-resistant] (PF-08, PFR 08001, PFR08026) – norepinephrine–dopamine releasing agent [30]
  • Dextroamphetamine sulfate [modified release capsules] (HLD-900, HLD-100) – norepinephrine–dopamine releasing agent [31]
  • Dopamine [intranasal] (DopaMat, MPP-18) – dopamine receptor agonist [32]
  • Eltoprazine (DU-28853) – serotonin 5-HT1A and 5-HT1B receptor agonist [33]
  • Fasoracetam [co-crystallised] (AEVI-004, NFC-1) – racetam / metabotropic glutamate receptor modulator [34]
  • GTS-21 (DMXB-A, DMXB-A sustained release, DMXB-A-SR) – α7 nicotinic acetylcholine receptor agonist [35]
  • Guanfacine [once-daily] (Guanfacine Carrier Wave, SPD-547) – α2-adrenergic receptor agonist [36]
  • IPX-233 (IPX233 ER C0003, IPX233-C0001, IPX233-C0002, IPX233-T0001, IPX233-T0002) – central nervous system stimulant [37]
  • Masupirdine (M1, M1 of SUVN-502, SUVN-502, SVN-502) – serotonin 5-HT6 receptor antagonist [38]
  • Methylphenidate [extended-release/abuse-resistant] (COL-171) – norepinephrine–dopamine reuptake inhibitor [39]
  • Methylphenidate [fast dissolve tablet] [Samyang Holdings Biopharmaceuticals] – norepinephrine–dopamine reuptake inhibitor [40]
  • Methylphenidate [transdermal system] (SHX-009) – norepinephrine–dopamine reuptake inhibitor [41] [42]
  • Methylphenidate/naltrexone (AVK-001) – norepinephrine–dopamine reuptake inhibitor and opioid receptor antagonist [43]
  • Nic-12 – undefined mechanism [44]
  • NLS-2 – antianaemic / heavy metal / iron replacement [45]
  • PD-3044 – dopamine reuptake inhibitor [46]
  • Pitolisant (tiprolisant; BF-2.649, BF-2649, Ozawade, Wakix) – histamine H3 receptor antagonist [47]
  • R-Sibutramine metabolite ((+)-desmethylsibutramine, (+)-didesmethylsibutramine, R-DDMS, R-desmethylsibutramine, R-didesmethylsibutramine) – serotonin–norepinephrine–dopamine reuptake inhibitor [48]
  • Selegiline [transdermal] (Emsam) – monoamine oxidase B inhibitor [49]
  • SKL-13865 (SKL-ADHD) – norepinephrine–dopamine reuptake inhibitor [50]
  • Sofinicline (A-422894.0, ABT-894) – α4β2 nicotinic acetylcholine receptor modulator [51]
  • SPN-811 – undefined mechanism [52]
  • Taminadenant (NIR-178, PBF-509) – adenosine A2A receptor antagonist [53]

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) [54]
  • 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 [55]
  • Norepinephrine reuptake inhibitors / adrenergic receptor antagonists [Pfizer] (NRI-022, NRI-193, WAY-253203, WAY-256805, WAY-260022, WAY-315193, WAY-318068) [56]
  • Pim2 / PolyPhetamine [ITL Pharma] [57]
  • Subtype-selective glutamate NMDA receptor modulators / glutamate NR2B receptor modulators [Novartis] [58]

Not under development

Development discontinued

  • ABT-418 – nicotinic acetylcholine receptor agonist [59]
  • Amphetamine [transdermal patch] [Noven/Takeda] – norepinephrine–dopamine releasing agent [60]
  • Ampreloxetine (TD-9855) – norepinephrine reuptake inhibitor [61]
  • AR-08 – adrenergic receptor agonist [62]
  • 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 [63]
  • AZD-5213 – histamine H3 receptor antagonist [64]
  • Bifemelane (SON-216) – monoamine oxidase inhibitor and weak norepinephrine reuptake inhibitor [65]
  • Bradanicline (ATA-101, TC-0569, TC-5619, TC-5619-238) – α7 nicotinic acetylcholine receptor agonist [66]
  • Brexpiprazole (Rexulti, Rxulti; Lu-AF41156, OPC-34712, OPDC-34712) – atypical antipsychotic / dopamine receptor partial agonist and serotonin receptor modulator [67]
  • Buspirone [transdermal] (BuSpar Patch) – serotonin 5-HT1A receptor partial agonist, other actions [68]
  • Cipralisant (GT-2331; Perceptin) – histamine H3 receptor antagonist [69]
  • CX-516 (1-BCP, AMPAlex, BDP-12, SPD-420) – ampakine / AMPA receptor modulator [70]
  • CX-1739 – ampakine / AMPA receptor modulator [71]
  • Donepezil (Aricept, Aricept D, Aricept Dry Syrup, Aricept Evess, Aricept ODT, Aricept SR, Donepezil SR, E-2020, E-2022, Eranz) – acetylcholinesterase inhibitor [72]
  • Droxidopa (3,4-dihydroxyphenylserine, 3,4-threo-DOPS, L-threo-dihydroxyphenylserine, L-threodops, Northera, threo-dopaserine, threo-DOPS) – prodrug of norepinephrine / adrenergic receptor agonist [73]
  • Fasoracetam (AEVI-001, LAM-105, MDGN-001, NFC-1, NS-105) – racetam / metabotropic glutamate receptor modulator [74]
  • Ispronicline (AZD-3480, RJR-1734, TC 01734, TC-1734, TC-1734-112) – α4β2-nicotinic acetylcholine receptor agonist [75]
  • KP-106 (dextroamphetamine prodrug oral film) – norepinephrine–dopamine releasing agent [76]
  • Lauflumide (flmodafinil, bisfluoromodafinil; NLS-14, NLS-4) – weak dopamine reuptake inhibitor, possibly other actions [77]
  • Manifaxine (BW-1555U88, GW-320659) – norepinephrine–dopamine reuptake inhibitor [78]
  • Mecamylamine (Inversine, Tridmac) – nicotinic acetylcholine receptor antagonist [79]
  • MEM-68626 – 5-HT6 receptor antagonist [80]
  • Metadoxine [sustained/extended-release] (pyridoxine-pyrrolidone carboxylate, pyridoxine pidolate; MDX, metadoxine SR, MG-01CI) – serotonin 5-HT2B receptor antagonist, GABA modulator, other actions [81]
  • Methylphenidate [transdermal patch] (TAH-9901) – norepinephrine–dopamine reuptake inhibitor [82]
  • MK-0249 – histamine H3 receptor antagonist [83]
  • Modafinil (AFT-801, Alertec, Attenace, CN-801, CRL-40476, Modasamil, Modasonil, Modavigil, Modiodal, Provigil, Sparlon, Vigil) – weak dopamine reuptake inhibitor, possibly other actions [84]
  • Nicotine/opipramol (ND-0801; opipramol/nicotine) – tricyclic antidepressant / monoamine and sigma receptor modulator and nicotinic acetylcholine receptor agonist [85]
  • NLS-8 – undefined mechanism [86]
  • NS-2359 (GSK-372475) – serotonin–norepinephrine–dopamine reuptake inhibitor [87]
  • OPC-64005 – serotonin–norepinephrine–dopamine reuptake inhibitor [88]
  • ORG-26576 (ORG26576) – ampakine / AMPA receptor modulator [89]
  • PF-3654746 (PF-03654746) – histamine H3 receptor antagonist [90]
  • Phacetoperane (NLS-3) – methylphenidate analogue / central nervous system stimulant / norepinephrine–dopamine reuptake inhibitor (?) [91]
  • Pirepemat (IRL-752) – "cortical enhancer" / serotonin 5-HT7 receptor antagonist and α2C-adrenergic receptor antagonist, other actions [92][3]
  • Pozanicline (A-87089.0, ABT-089) – α4β2 nicotinic acetylcholine receptor agonist [93]
  • SEP-225432 – serotonin–norepinephrine–dopamine reuptake inhibitor [94]
  • SGS-742 (CGP-36742, DVD-742, Lu-AE58479, SGS-742) – GABAB receptor antagonist [95]
  • SPD-483 – undefined mechanism [96]
  • SPD-554 (Guanfacine Carrier Wave project) – α2-adrenergic receptor agonist [97]
  • SPI-339 (NEO-339) – undefined mechanism [98]
  • TAK-137 – AMPA receptor potentiator [99]
  • TC-6683 (AZD 1446, TC-6683) – α4β2 nicotinic acetylcholine receptor agonist [100]
  • Tipepidine [sustained-release] (TS-141) – GIRK inhibitor [101]
  • Vortioxetine (Brintellix, LU-AA21004, LuAA 21004, Trintellix) – antidepressant / serotonin reuptake inhibitor and serotonin receptor modulator [102]

Research programmes

  • Potassium channel modulators [Astellas Pharma/Icagen] [103]

Formal development never or not yet started

Clinically used drugs

Approved drugs

Norepinephrine–dopamine releasing agents

Norepinephrine–dopamine reuptake inhibitors

Norepinephrine reuptake inhibitors

α2-Adrenergic receptor agonists

Off-label drugs

See also

References

  1. ^ Ceresoli-Borroni G, Nasser A, Adewole T, Liranso T, Xu J, Schwabe S, Findling RL (September 2021). "A Double-Blind, Randomized Study of Extended-Release Molindone for Impulsive Aggression in ADHD". J Atten Disord. 25 (11): 1564–1577. doi:10.1177/1087054720909084. PMID 32338106. S2CID 216556900.
  2. ^ Robb AS, Connor DF, Amann BH, Vitiello B, Nasser A, O'Neal W, Schwabe S, Ceresoli-Borroni G, Newcorn JH, Candler SA, Buitelaar JK, Findling RL (March 2020). "Closing the gap: unmet needs of individuals with impulsive aggressive behavior observed in children and adolescents". CNS Spectr. 26 (5): 448–456. doi:10.1017/S1092852920001224. PMID 32228725. S2CID 214750205.
  3. ^ Hjorth S, Waters S, Waters N, Tedroff J, Svensson P, Fagerberg A, Edling M, Svanberg B, Ljung E, Gunnergren J, McLean SL, Grayson B, Idris NF, Neill JC, Sonesson C (September 2020). "(3S)-3-(2,3-difluorophenyl)-3-methoxypyrrolidine (IRL752) -a Novel Cortical-Preferring Catecholamine Transmission- and Cognition-Promoting Agent". J Pharmacol Exp Ther. 374 (3): 404–419. doi:10.1124/jpet.120.000037. hdl:10454/17970. PMID 32605972. S2CID 220283184.
  4. ^ Wilens TE, Morrison NR, Prince J (October 2011). "An update on the pharmacotherapy of attention-deficit/hyperactivity disorder in adults". Expert Rev Neurother. 11 (10): 1443–65. doi:10.1586/ern.11.137. PMC 3229037. PMID 21955201.
  5. ^ a b c Kooij JJ, Bijlenga D, Salerno L, Jaeschke R, Bitter I, Balázs J, Thome J, Dom G, Kasper S, Nunes Filipe C, Stes S, Mohr P, Leppämäki S, Casas M, Bobes J, Mccarthy JM, Richarte V, Kjems Philipsen A, Pehlivanidis A, Niemela A, Styr B, Semerci B, Bolea-Alamanac B, Edvinsson D, Baeyens D, Wynchank D, Sobanski E, Philipsen A, McNicholas F, Caci H, Mihailescu I, Manor I, Dobrescu I, Saito T, Krause J, Fayyad J, Ramos-Quiroga JA, Foeken K, Rad F, Adamou M, Ohlmeier M, Fitzgerald M, Gill M, Lensing M, Motavalli Mukaddes N, Brudkiewicz P, Gustafsson P, Tani P, Oswald P, Carpentier PJ, De Rossi P, Delorme R, Markovska Simoska S, Pallanti S, Young S, Bejerot S, Lehtonen T, Kustow J, Müller-Sedgwick U, Hirvikoski T, Pironti V, Ginsberg Y, Félegyházy Z, Garcia-Portilla MP, Asherson P (February 2019). "Updated European Consensus Statement on diagnosis and treatment of adult ADHD". Eur Psychiatry. 56: 14–34. doi:10.1016/j.eurpsy.2018.11.001. hdl:10651/51910. PMID 30453134.
  6. ^ a b c 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.

Further reading

External links


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