Fasoracetam

Last updated

Fasoracetam
Fasoracetam.svg
Fasoracetam3d.png
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 class Racetam
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US:Not FDA-approved
Pharmacokinetic data
Bioavailability 79–97% (animals) [1]
Elimination half-life 4–6.5 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
Formula C10H16N2O2
Molar mass 196.250 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 Yes check.svgY
  • Key:GOWRRBABHQUJMX-MRVPVSSYSA-N Yes check.svgY
   (verify)

Fasoracetam (INN Tooltip 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]

Contents

Pharmacology

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

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

History

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

Legality

Australia

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

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 AFEVI-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]

The results of clinical studies for ADHD with fasoracetam have not shown statistical significance in efficacy. [4]

References

  1. 1 2 3 4 5 6 7 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.
  2. 1 2 Gualtieri F, Manetti D, Romanelli MN, Ghelardini C (2002). "Design and study of piracetam-like nootropics, controversial members of the problematic class of cognition-enhancing drugs". Current Pharmaceutical Design. 8 (2): 125–138. doi:10.2174/1381612023396582. PMID   11812254.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 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. 1 2 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. 1 2 3 4 "Fasoracetam - Avalo Therapeutics". AdisInsight. Springer Nature Switzerland AG. 30 August 2021. Retrieved 1 October 2024.
  6. 1 2 3 4 "Fasoracetam - Nobias Therapeutics". AdisInsight. Springer Nature Switzerland AG. 17 October 2023. Retrieved 1 October 2024.
  7. 1 2 3 4 "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.
  9. 1 2 Moskowitz DH (2017). Finding the Genetic Cause and Therapy for ADHD, Autism and 22q. BookBaby (self published). ISBN   9781483590981.
  10. 1 2 3 Sharma, B. (7 October 2016). "Medgenics: NFC-1 Could Be A Key Future Revenue Driver". Seeking Alpha.
  11. ↑ "Press Release: Medgenics, Inc. Announces Name Change to Aevi Genomic Medicine, Inc". Aevi via MarketWired. 16 December 2016.
  12. 1 2 Elia J, Ungal G, Kao C, Ambrosini A, De Jesus-Rosario N, Larsen L, et al. (January 2018). "Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling". Nature Communications. 9 (1) 4. Bibcode:2018NatCo...9....4E. doi:10.1038/s41467-017-02244-2. PMC   5770454 . PMID   29339723.
  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. 1 2 Poisons Standard February 2020. comlaw.gov.au
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