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{{Short description|Chemical compound}}
{{chembox
{{cs1 config|name-list-style=vanc|display-authors=6}}
| Verifiedfields = changed
{{Infobox drug
| Watchedfields = changed
| Verifiedfields = verified
| Watchedfields = verified
| verifiedrevid = 444354364
| verifiedrevid = 444354364
| drug_name =
| ImageFileL1 = Fasoracetam.svg
| image = Fasoracetam.svg
| ImageSizeL1 = 125px
| width = 200px
| ImageFileR1 = Fasoracetam3d.png
| image2 = Fasoracetam3d.png
| ImageSizeR1 = 100px
| width2 = 125px
| IUPACName = (5''R'')-5-(Piperidine-1-carbonyl)pyrrolidin-2-one
| caption =
| OtherNames = (5''R'')-5-Oxo-<small>D</small>-prolinepiperidinamide monohydrate, NS-105, AEVI-001, LAM 105, MDGN-001, NFC 1<ref>[http://fdasis.nlm.nih.gov/srs/ProxyServlet?mergeData=true&objectHandle=DBMaint&APPLICATION_NAME=fdasrs&actionHandle=default&nextPage=jsp/srs/ResultScreen.jsp&TXTSUPERLISTID=42O8UF5CJB&QV1=42O8UF5CJB FDA/NIH Substance registration system]. Page accessed March 21, 2016</ref><ref name=adis>{{cite web |url=http://adisinsight.springer.com/drugs/800003134|title=Drug Profile Fasoracetam }}</ref>

|Section1={{Chembox Identifiers
<!-- Clinical data -->
| pronounce =
| tradename =
| Drugs.com =
| MedlinePlus =
| licence_CA =
| licence_EU =
| DailyMedID =
| licence_US =
| pregnancy_AU =
| pregnancy_category =
| dependency_liability =
| addiction_liability =
| routes_of_administration = [[Oral administration|Oral]]
| class = [[Racetam]]
| ATC_prefix =
| ATC_suffix =

<!-- Legal status -->
| legal_US = Not FDA-approved
| legal_AU = S4
| legal_status =

<!-- Pharmacokinetic data -->
| bioavailability = 79–97% (animals)<ref name="Malykh2010" />
| protein_bound =
| metabolism =
| metabolites =
| onset =
| elimination_half-life = 4–6.5{{nbsp}}hours<ref name="Malykh2010" />
| duration_of_action =
| excretion =

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 110958-19-5
| CAS_supplemental =
| PubChem = 198695
| PubChem = 198695
| IUPHAR_ligand =
| DrugBank = DB16163
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 171980
| ChemSpiderID = 171980
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| UNII_Ref = {{fdacite|correct|FDA}}
| ChEMBL = 2106179
| UNII = 42O8UF5CJB
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = C13311
| KEGG = C13311
| ChEBI = 31592
| InChI = 1/C10H16N2O2/c13-9-5-4-8(11-9)10(14)12-6-2-1-3-7-12/h8H,1-7H2,(H,11,13)/t8-/m1/s1
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| InChIKey = GOWRRBABHQUJMX-MRVPVSSYBL
| ChEMBL = 2106179
| NIAID_ChemDB =
| PDB_ligand =
| synonyms = AEVI-001; AEVI-004; LAM-105; MDGN-001; NB-001; NFC-1; NS-105; (5''R'')-5-Oxo-<small>D</small>-prolinepiperidinamide

<!-- Chemical data -->
| IUPAC_name = (5''R'')-5-(piperidine-1-carbonyl)pyrrolidin-2-one
| C=10 | H=16 | N=2 | O=2
| SMILES = C1CCN(CC1)C(=O)[C@H]2CCC(=O)N2
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C10H16N2O2/c13-9-5-4-8(11-9)10(14)12-6-2-1-3-7-12/h8H,1-7H2,(H,11,13)/t8-/m1/s1
| StdInChI = 1S/C10H16N2O2/c13-9-5-4-8(11-9)10(14)12-6-2-1-3-7-12/h8H,1-7H2,(H,11,13)/t8-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = GOWRRBABHQUJMX-MRVPVSSYSA-N
| StdInChIKey = GOWRRBABHQUJMX-MRVPVSSYSA-N
| CASNo_Ref = {{cascite|correct|??}}
| CASNo =110958-19-5
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 42O8UF5CJB
| SMILES= O=C(N1CCCCC1)[C@@H]2NC(=O)CC2 }}
|Section2={{Chembox Properties
| C=10 | H=16 | N=2 | O=2
| Appearance =
| Density =
| MeltingPt =
| BoilingPt =
| Solubility = }}
|Section5={{Chembox Pharmacology
| AdminRoutes = Oral
| Bioavail =
| Metabolism =
| HalfLife =
| ProteinBound =
| Excretion =
| Legal_status =
| Legal_US = Not FDA approved
| Legal_UK =
| Legal_AU = S4
| Legal_CA =
| Pregnancy_category =
| Pregnancy_AU =
}}
}}
}}


'''Fasoracetam''' ({{Abbrlink|INN|International Nonproprietary Name}}) is an [[experimental drug]] of the [[racetam]] group which was never marketed.<ref name="Malykh2010">{{cite journal | vauthors = Malykh AG, Sadaie MR | title = Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders | journal = Drugs | volume = 70 | issue = 3 | pages = 287–312 | date = February 2010 | pmid = 20166767 | doi = 10.2165/11319230-000000000-00000 | s2cid = 12176745 }}</ref><ref name="GualtieriManettiRomanelli2002">{{cite journal | vauthors = Gualtieri F, Manetti D, Romanelli MN, Ghelardini C | title = Design and study of piracetam-like nootropics, controversial members of the problematic class of cognition-enhancing drugs | journal = Current Pharmaceutical Design | volume = 8 | issue = 2 | pages = 125–138 | date = 2002 | pmid = 11812254 | doi = 10.2174/1381612023396582 }}</ref><ref name="ConnollyGlessnerKao2015">{{cite journal | vauthors = Connolly JJ, Glessner JT, Elia J, Hakonarson H | title = ADHD & Pharmacotherapy: Past, Present and Future: A Review of the Changing Landscape of Drug Therapy for Attention Deficit Hyperactivity Disorder | journal = Therapeutic Innovation & Regulatory Science | volume = 49 | issue = 5 | pages = 632–642 | date = September 2015 | pmid = 26366330 | pmc = 4564067 | doi = 10.1177/2168479015599811 }}</ref> It is a putative [[nootropic]] that failed to show sufficient [[efficacy]] in [[clinical trial]]s for [[vascular dementia]].<ref name="ConnollyGlessnerKao2015" /> The drug was also subsequently [[drug repurposing|repurposed]] for treatment of a variety of other conditions, such as [[attention deficit hyperactivity disorder]] (ADHD), but effectiveness for ADHD was disappointing<ref name="NageyeCortese2019" /> and development of fasoracetam for most other conditions has been discontinued as well.<ref name="AdisInsight-Avalo" /><ref name="AdisInsight-Nobias" /><ref name="AdisInsight-Avalo-Co-Crystal" /><ref>{{cite journal|title=Recommended INN List 40|journal=WHO Drug Information|date=1998|volume=12|issue=2|url=https://mednet-communities.net/inn/db/media/docs/r-innlist40.pdf}}</ref> In any case, it remains under development for treatment of [[DiGeorge syndrome]].<ref name="AdisInsight-Nobias" />
'''Fasoracetam''' is a [[research chemical]] of the [[racetam]] family.<ref>{{cite web |url=https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=198695|title=5-oxo-D-prolinepiperidinamide monohydrate - Compound Summary|access-date=21 July 2013}}</ref> It is a putative [[nootropic]] that failed to show sufficient [[efficacy]] in clinical trials for [[vascular dementia]]. It is currently being studied for its potential use for [[attention deficit hyperactivity disorder]].<ref name=adis/><ref>{{cite journal|title=Recommended INN List 40|journal=WHO Drug Information|date=1998|volume=12|issue=2|url=https://mednet-communities.net/inn/db/media/docs/r-innlist40.pdf}}</ref>


==Pharmacology==
Fasoracetam appears to agonize all three groups of [[metabotropic glutamate receptor]]s and has improved cognitive function in [[animal testing on rodents|rodent studies]].<ref name=Connolly/> It is [[orally bioavailable]] and is excreted mostly unchanged via the urine.<ref>{{cite journal|last1=Malykh|first1=AG|last2=Sadaie|first2=MR|title=Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders.|journal=Drugs|date=12 February 2010|volume=70|issue=3|pages=287–312|doi=10.2165/11319230-000000000-00000|pmid=20166767}}</ref>
Fasoracetam appears to modulate and stimulate all three groups of [[metabotropic glutamate receptor]]s (mGluRs).<ref name="ConnollyGlessnerKao2015" /><ref name="Malykh2010" /> It has been found to improve certain aspects of cognitive function in [[animal testing on rodents|rodent studies]].<ref name="ConnollyGlessnerKao2015" /><ref name="Malykh2010" /> The drug is [[orally bioavailable]] and is [[excretion|excreted]] mostly unchanged in [[urine]].<ref name="Malykh2010" /><ref name="ConnollyGlessnerKao2015" />


==Chemistry==
Fasoracetam was discovered by scientists at the Japanese pharmaceutical company [[Nippon Shinyaku]], which brought it through Phase 3 clinical trials for [[vascular dementia]], and abandoned it due to lack of efficacy.<ref name=Connolly>{{cite journal |title=ADHD & Pharmacotherapy: Past, Present and Future: A Review of the Changing Landscape of Drug Therapy for Attention Deficit Hyperactivity Disorder. | volume=49 | issue=5 | journal=Ther Innov Regul Sci | pages=632–642 | last1 = Connolly| first1 = J | last2 = Glessner | first2 = J | last3 = Kao | first3 = C | last4 = Elia | first4 = J | last5 = Hakonarson | first5 = H | doi=10.1177/2168479015599811|pmid=26366330|pmc=4564067}}</ref><ref name=Hoskowitz>{{cite book|last1=Moskowitz|first1=D. H.|title=Finding the Genetic Cause and Therapy for ADHD, Autism and 22q|date=2017|publisher=BookBaby (self published)|isbn=9781483590981|url=https://books.google.com/books?id=LSrlDQAAQBAJ&pg=PT117|language=en}}</ref>
Fasoracetam is a [[racetam]] and a [[chemical derivative|derivative]] of [[pyroglutamic acid]].<ref name="Malykh2010" /><ref name="GualtieriManettiRomanelli2002" />


==History==
Scientists at [[Children's Hospital of Philadelphia]] led by Hakon Hakonarson have studied fasoracetam's potential use in [[attention deficit hyperactivity disorder]].<ref name=Connolly/> Hakonarson started a company called neuroFix Therapeutics to try to bring the drug to market for this use; neuroFix acquired Nippon Shinyaku's clinical data as part of its efforts.<ref name=Hoskowitz/><ref name=Alpha/> neuroFix was acquired by Medgenics in 2015.<ref name=Alpha/> Medgenics changed its name to Aevi Genomic Medicine in 2016.<ref>{{cite web | title=Press Release: Medgenics, Inc. Announces Name Change to Aevi Genomic Medicine, Inc. | url=http://www.prnewswire.com/news-releases/medgenics-inc-announces-name-change-to-aevi-genomic-medicine-inc-300378599.html | publisher=Aevi via MarketWired|date=16 December 2016}}</ref> Clinical trials in adolescents with ADHD who also have mGluR mutations started in 2016.<ref name=Alpha>{{cite web | title=Medgenics: NFC-1 Could Be A Key Future Revenue Driver. | url=https://seekingalpha.com/article/4010894-medgenics-nfcminus-1-key-future-revenue-driver | author=Sharma, B.}}</ref> While Fasoracetam may be effective in the treatment of ADHD in people with specific mGluR mutations, these represent around 10% of total ADHD cases, and Fasoracetam is likely ineffective in all other cases.<ref>{{Cite web|title=(PDF) Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling|url=https://www.researchgate.net/publication/322527361_Fasoracetam_in_adolescents_with_ADHD_and_glutamatergic_gene_network_variants_disrupting_mGluR_neurotransmitter_signaling|access-date=2020-10-16|website=ResearchGate|language=en}}</ref><ref>{{Cite web|last=Tardner|first=P|title=Fasoracetam as a treatment for ADHD: A systematic review of available clinical data • International Journal of Environmental Science & Technology|url=https://www.ijest.org/fasoracetam-treatment-adhd-a-systematic-review/|url-status=live|archive-date=2020-09-09|access-date=2020-10-16|website=International Journal of Environmental Science & Technology|language=en-US}}</ref> Studies showing improvements in cognitive function from Fasoracteam have exclusively been done on rodents.<ref>{{Cite journal|last=Elia|first=Josephine|last2=Ungal|first2=Grace|last3=Kao|first3=Charlly|last4=Ambrosini|first4=Alexander|last5=De Jesus-Rosario|first5=Nilsa|last6=Larsen|first6=Lene|last7=Chiavacci|first7=Rosetta|last8=Wang|first8=Tiancheng|last9=Kurian|first9=Christine|last10=Titchen|first10=Kanani|last11=Sykes|first11=Brian|date=2018-01-16|title=Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5770454/|journal=Nature Communications|volume=9|doi=10.1038/s41467-017-02244-2|issn=2041-1723|pmc=5770454|pmid=29339723}}</ref>
Fasoracetam was developed in the late 1980s.<ref name="ConnollyGlessnerKao2015" /> It was discovered by scientists at the Japanese pharmaceutical company Nippon Shinyaku, which brought it through [[phases of clinical research|Phase 3 clinical trials]] for [[vascular dementia]], and abandoned it due to lack of [[efficacy]].<ref name="ConnollyGlessnerKao2015" /><ref name="Hoskowitz2017">{{cite book|last1=Moskowitz|first1=D. H.|title=Finding the Genetic Cause and Therapy for ADHD, Autism and 22q|date=2017|publisher=BookBaby (self published)|isbn=9781483590981|url=https://books.google.com/books?id=LSrlDQAAQBAJ&pg=PT117|language=en}}</ref> Subsequently, fasoracetam was repurposed for treatment of ADHD and other indications.<ref name="ConnollyGlessnerKao2015" /><ref name="AdisInsight-Avalo" /><ref name="AdisInsight-Nobias" /><ref name="AdisInsight-Avalo-Co-Crystal" />


Scientists at [[Children's Hospital of Philadelphia]] led by Hakon Hakonarson have studied fasoracetam's potential use in [[attention deficit hyperactivity disorder]].<ref name="ConnollyGlessnerKao2015" /> Hakonarson's company neuroFix tried to bring the drug to market for this use; neuroFix acquired Nippon Shinyaku's clinical data as part of its efforts.<ref name="Hoskowitz2017" /><ref name="SeekingAlpha2016" /> neuroFix was acquired by Medgenics in 2015.<ref name="SeekingAlpha2016" /> Medgenics changed its name to Aevi Genomic Medicine in 2016.<ref>{{cite web | title=Press Release: Medgenics, Inc. Announces Name Change to Aevi Genomic Medicine, Inc. | url=http://www.prnewswire.com/news-releases/medgenics-inc-announces-name-change-to-aevi-genomic-medicine-inc-300378599.html | publisher=Aevi via MarketWired|date=16 December 2016}}</ref>
== Legality ==
=== Australia ===
Fasoracetam is a schedule 4 substance in Australia under the [[Standard for the Uniform Scheduling of Medicines and Poisons|Poisons Standard (February 2020)]].<ref name="Poisons Stanrard">[https://www.legislation.gov.au/Details/F2020C00148 Poisons Standard February 2020]. comlaw.gov.au</ref> A schedule 4 substance is classified as "Prescription Only Medicine, or Prescription Animal Remedy – Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription." <ref name="Poisons Stanrard" />


Clinical trials in adolescents with ADHD who also have mGluR mutations started in 2016.<ref name="SeekingAlpha2016">{{cite news | title=Medgenics: NFC-1 Could Be A Key Future Revenue Driver. | url=https://seekingalpha.com/article/4010894-medgenics-nfcminus-1-key-future-revenue-driver | author=Sharma, B.| newspaper=Seeking Alpha | date=7 October 2016 }}</ref> While fasoracetam may be effective in the treatment of ADHD in people with specific mGluR mutations, these represent around 10% of total ADHD cases, and fasoracetam is likely ineffective in all other cases.<ref name="pmid29339723"/><ref>{{Cite journal|last=Tardner|first=P|title=Fasoracetam as a treatment for ADHD: A systematic review of available clinical data|url=https://www.ijest.org/fasoracetam-treatment-adhd-a-systematic-review/|date=2020-09-09|journal=International Journal of Environmental Science & Technology|language=en-US}}</ref> Studies showing improvements in cognitive function from fasoracetam have exclusively been done on rodents.<ref name="pmid29339723">{{cite journal | vauthors = Elia J, Ungal G, Kao C, Ambrosini A, De Jesus-Rosario N, Larsen L, Chiavacci R, Wang T, Kurian C, Titchen K, Sykes B, Hwang S, Kumar B, Potts J, Davis J, Malatack J, Slattery E, Moorthy G, Zuppa A, Weller A, Byrne E, Li YR, Kraft WK, Hakonarson H | title = Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling | journal = Nature Communications | volume = 9 | issue = 1 | pages = 4 | date = January 2018 | pmid = 29339723 | pmc = 5770454 | doi = 10.1038/s41467-017-02244-2 | bibcode = 2018NatCo...9....4E }}</ref>
==See also==
* [[Drug repositioning]]


==Society and culture==
==References==
===Legality===
{{reflist}}
====Australia====
Fasoracetam is a schedule 4 substance in Australia under the [[Standard for the Uniform Scheduling of Medicines and Poisons|Poisons Standard (February 2020)]].<ref name="PoisonsStandard2020">[https://www.legislation.gov.au/Details/F2020C00148 Poisons Standard February 2020]. comlaw.gov.au</ref> A schedule 4 substance is classified as "Prescription Only Medicine, or Prescription Animal Remedy – Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription."<ref name="PoisonsStandard2020" />

==Research==
Fasoracetam was originally developed for treatment of [[cognitive impairment]] related to [[dementia]].<ref name="ConnollyGlessnerKao2015" /> It reached [[Phases of clinical research#Phase III|phase 3]] [[clinical trial]]s for this indication.<ref name="ConnollyGlessnerKao2015" /> However, development was discontinued due to lack of effectiveness and fasoracetam was never marketed.<ref name="ConnollyGlessnerKao2015" />

Fasoracetam (developmental code names AEVI-001, LAM-105, MDGN-001, NFC-1, NS-105) was under development by Avalo Therapeutics (previously Cerecor) for the treatment of [[attention deficit hyperactivity disorder]] (ADHD), [[autistic disorder]], [[cognition disorder]]s, [[DiGeorge syndrome]], and [[major depressive disorder]].<ref name="AdisInsight-Avalo">{{cite web | title=Fasoracetam - Avalo Therapeutics | work = AdisInsight | publisher = Springer Nature Switzerland AG | date=30 August 2021 | url=https://adisinsight.springer.com/drugs/800003134 | access-date=1 October 2024}}</ref> However, development for all indications was discontinued by 2018.<ref name="AdisInsight-Avalo" /> The drug (developmental code name NB-001) is also under development by Nobias Therapeutics for the treatment of DiGeorge syndrome and is in [[Phases of clinical research#Phase II|phase 2]] [[clinical trial]]s for this use as of October 2023.<ref name="AdisInsight-Nobias">{{cite web | title=Fasoracetam - Nobias Therapeutics | work = AdisInsight | publisher = Springer Nature Switzerland AG | date=17 October 2023 | url=https://adisinsight.springer.com/drugs/800067855 | access-date=1 October 2024}}</ref> A [[cocrystal|co-crystallized]] form of fasoracetam (developmental code name AEVI-004) is under development by Avalo Therapeutics for the treatment of ADHD, autistic disorder, and [[epilepsy]] as well.<ref name="AdisInsight-Avalo-Co-Crystal">{{cite web | title=Co-crystallised fasoracetam - Avalo Therapeutics | work = AdisInsight | publisher = Springer Nature Switzerland AG | date=28 April 2023 | url=https://adisinsight.springer.com/drugs/800052566 | access-date=1 October 2024}}</ref> However, no recent development has been reported for these indications as of April 2023.<ref name="AdisInsight-Avalo-Co-Crystal" /> Pharmaceutical developmental code names of fasoracetam include

The results of clinical studies of fasoracetam for ADHD have been disappointing.<ref name="NageyeCortese2019">{{cite journal | vauthors = Nageye F, Cortese S | title = Beyond stimulants: a systematic review of randomised controlled trials assessing novel compounds for ADHD | journal = Expert Review of Neurotherapeutics | volume = 19 | issue = 7 | pages = 707–717 | date = July 2019 | pmid = 31167583 | doi = 10.1080/14737175.2019.1628640 | url = https://eprints.soton.ac.uk/431813/1/ERN_main_text_R1_BLACK.doc }}</ref>

== References ==
{{Reflist}}


{{Racetams}}
{{Racetams}}


[[Category:Racetams]]
[[Category:1-Piperidinyl compounds]]
[[Category:Piperidines]]
[[Category:Carboxamides]]
[[Category:Carboxamides]]
[[Category:Drugs with unknown mechanisms of action]]
[[Category:Experimental drugs]]
[[Category:Nootropics]]
[[Category:Nootropics]]
[[Category:Racetams]]

Latest revision as of 08:36, 3 October 2024

Fasoracetam
Clinical data
Other namesAEVI-001; AEVI-004; LAM-105; MDGN-001; NB-001; NFC-1; NS-105; (5R)-5-Oxo-D-prolinepiperidinamide
Routes of
administration		Oral
Drug classRacetam
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: Not FDA-approved
Pharmacokinetic data
Bioavailability79–97% (animals)[1]
Elimination half-life4–6.5 hours[1]
Identifiers
  • (5R)-5-(piperidine-1-carbonyl)pyrrolidin-2-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC10H16N2O2
Molar mass196.250 g·mol−1
3D model (JSmol)
  • C1CCN(CC1)C(=O)[C@H]2CCC(=O)N2
  • InChI=1S/C10H16N2O2/c13-9-5-4-8(11-9)10(14)12-6-2-1-3-7-12/h8H,1-7H2,(H,11,13)/t8-/m1/s1 checkY
  • Key:GOWRRBABHQUJMX-MRVPVSSYSA-N checkY
  (verify)

Fasoracetam (INNTooltip International Nonproprietary Name) is an experimental drug of the racetam group which was never marketed.[1][2][3] It is a putative nootropic that failed to show sufficient efficacy in clinical trials for vascular dementia.[3] The drug was also subsequently repurposed for treatment of a variety of other conditions, such as attention deficit hyperactivity disorder (ADHD), but effectiveness for ADHD was disappointing[4] and development of fasoracetam for most other conditions has been discontinued as well.[5][6][7][8] In any case, it remains under development for treatment of DiGeorge syndrome.[6]

Pharmacology

[edit]

Fasoracetam appears to modulate and stimulate all three groups of metabotropic glutamate receptors (mGluRs).[3][1] It has been found to improve certain aspects of cognitive function in rodent studies.[3][1] The drug is orally bioavailable and is excreted mostly unchanged in urine.[1][3]

Chemistry

[edit]

Fasoracetam is a racetam and a derivative of pyroglutamic acid.[1][2]

History

[edit]

Fasoracetam was developed in the late 1980s.[3] It was discovered by scientists at the Japanese pharmaceutical company Nippon Shinyaku, which brought it through Phase 3 clinical trials for vascular dementia, and abandoned it due to lack of efficacy.[3][9] Subsequently, fasoracetam was repurposed for treatment of ADHD and other indications.[3][5][6][7]

Scientists at Children's Hospital of Philadelphia led by Hakon Hakonarson have studied fasoracetam's potential use in attention deficit hyperactivity disorder.[3] Hakonarson's company neuroFix tried to bring the drug to market for this use; neuroFix acquired Nippon Shinyaku's clinical data as part of its efforts.[9][10] neuroFix was acquired by Medgenics in 2015.[10] Medgenics changed its name to Aevi Genomic Medicine in 2016.[11]

Clinical trials in adolescents with ADHD who also have mGluR mutations started in 2016.[10] While fasoracetam may be effective in the treatment of ADHD in people with specific mGluR mutations, these represent around 10% of total ADHD cases, and fasoracetam is likely ineffective in all other cases.[12][13] Studies showing improvements in cognitive function from fasoracetam have exclusively been done on rodents.[12]

Society and culture

[edit]

Legality

[edit]

Australia

[edit]

Fasoracetam is a schedule 4 substance in Australia under the Poisons Standard (February 2020).[14] A schedule 4 substance is classified as "Prescription Only Medicine, or Prescription Animal Remedy – Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription."[14]

Research

[edit]

Fasoracetam was originally developed for treatment of cognitive impairment related to dementia.[3] It reached phase 3 clinical trials for this indication.[3] However, development was discontinued due to lack of effectiveness and fasoracetam was never marketed.[3]

Fasoracetam (developmental code names AEVI-001, LAM-105, MDGN-001, NFC-1, NS-105) was under development by Avalo Therapeutics (previously Cerecor) for the treatment of attention deficit hyperactivity disorder (ADHD), autistic disorder, cognition disorders, DiGeorge syndrome, and major depressive disorder.[5] However, development for all indications was discontinued by 2018.[5] The drug (developmental code name NB-001) is also under development by Nobias Therapeutics for the treatment of DiGeorge syndrome and is in phase 2 clinical trials for this use as of October 2023.[6] A co-crystallized form of fasoracetam (developmental code name AEVI-004) is under development by Avalo Therapeutics for the treatment of ADHD, autistic disorder, and epilepsy as well.[7] However, no recent development has been reported for these indications as of April 2023.[7] Pharmaceutical developmental code names of fasoracetam include

The results of clinical studies of fasoracetam for ADHD have been disappointing.[4]

References

[edit]
  1. ^ a b c d e f g Malykh AG, Sadaie MR (February 2010). "Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders". Drugs. 70 (3): 287–312. doi:10.2165/11319230-000000000-00000. PMID 20166767. S2CID 12176745.
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  3. ^ a b c d e f g h i j k l Connolly JJ, Glessner JT, Elia J, Hakonarson H (September 2015). "ADHD & Pharmacotherapy: Past, Present and Future: A Review of the Changing Landscape of Drug Therapy for Attention Deficit Hyperactivity Disorder". Therapeutic Innovation & Regulatory Science. 49 (5): 632–642. doi:10.1177/2168479015599811. PMC 4564067. PMID 26366330.
  4. ^ a b Nageye F, Cortese S (July 2019). "Beyond stimulants: a systematic review of randomised controlled trials assessing novel compounds for ADHD". Expert Review of Neurotherapeutics. 19 (7): 707–717. doi:10.1080/14737175.2019.1628640. PMID 31167583.
  5. ^ a b c d "Fasoracetam - Avalo Therapeutics". AdisInsight. Springer Nature Switzerland AG. 30 August 2021. Retrieved 1 October 2024.
  6. ^ a b c d "Fasoracetam - Nobias Therapeutics". AdisInsight. Springer Nature Switzerland AG. 17 October 2023. Retrieved 1 October 2024.
  7. ^ a b c d "Co-crystallised fasoracetam - Avalo Therapeutics". AdisInsight. Springer Nature Switzerland AG. 28 April 2023. Retrieved 1 October 2024.
  8. ^ "Recommended INN List 40" (PDF). WHO Drug Information. 12 (2). 1998.
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  13. ^ Tardner P (2020-09-09). "Fasoracetam as a treatment for ADHD: A systematic review of available clinical data". International Journal of Environmental Science & Technology.
  14. ^ a b Poisons Standard February 2020. comlaw.gov.au
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