Chemistry:Fasoracetam

From HandWiki

Fasoracetam (INN) 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

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. ↑ 1.0 1.1 1.2 1.3 1.4 "Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders". Drugs 70 (3): 287–312. February 2010. doi:10.2165/11319230-000000000-00000. PMID 20166767. 
  2. ↑ 2.0 2.1 "Design and study of piracetam-like nootropics, controversial members of the problematic class of cognition-enhancing drugs". Current Pharmaceutical Design 8 (2): 125–138. 2002. doi:10.2174/1381612023396582. PMID 11812254. 
  3. ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 "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. September 2015. doi:10.1177/2168479015599811. PMID 26366330. 
  4. ↑ 4.0 4.1 "Beyond stimulants: a systematic review of randomised controlled trials assessing novel compounds for ADHD". Expert Review of Neurotherapeutics 19 (7): 707–717. July 2019. doi:10.1080/14737175.2019.1628640. PMID 31167583. https://eprints.soton.ac.uk/431813/1/ERN_main_text_R1_BLACK.doc. 
  5. ↑ 5.0 5.1 5.2 5.3 "Fasoracetam - Avalo Therapeutics". AdisInsight. Springer Nature Switzerland AG. 30 August 2021. https://adisinsight.springer.com/drugs/800003134. 
  6. ↑ 6.0 6.1 6.2 6.3 "Fasoracetam - Nobias Therapeutics". AdisInsight. Springer Nature Switzerland AG. 17 October 2023. https://adisinsight.springer.com/drugs/800067855. 
  7. ↑ 7.0 7.1 7.2 7.3 "Co-crystallised fasoracetam - Avalo Therapeutics". AdisInsight. Springer Nature Switzerland AG. 28 April 2023. https://adisinsight.springer.com/drugs/800052566. 
  8. ↑ "Recommended INN List 40". WHO Drug Information 12 (2). 1998. https://mednet-communities.net/inn/db/media/docs/r-innlist40.pdf. 
  9. ↑ 9.0 9.1 Moskowitz, D. H. (2017) (in en). Finding the Genetic Cause and Therapy for ADHD, Autism and 22q. BookBaby (self published). ISBN 9781483590981. https://books.google.com/books?id=LSrlDQAAQBAJ&pg=PT117. 
  10. ↑ 10.0 10.1 10.2 Sharma, B. (7 October 2016). "Medgenics: NFC-1 Could Be A Key Future Revenue Driver.". Seeking Alpha. https://seekingalpha.com/article/4010894-medgenics-nfcminus-1-key-future-revenue-driver. 
  11. ↑ "Press Release: Medgenics, Inc. Announces Name Change to Aevi Genomic Medicine, Inc.". Aevi via MarketWired. 16 December 2016. http://www.prnewswire.com/news-releases/medgenics-inc-announces-name-change-to-aevi-genomic-medicine-inc-300378599.html. 
  12. ↑ 12.0 12.1 "Fasoracetam in adolescents with ADHD and glutamatergic gene network variants disrupting mGluR neurotransmitter signaling". Nature Communications 9 (1). January 2018. doi:10.1038/s41467-017-02244-2. PMID 29339723. Bibcode: 2018NatCo...9....4E. 
  13. ↑ Tardner, P (2020-09-09). "Fasoracetam as a treatment for ADHD: A systematic review of available clinical data" (in en-US). International Journal of Environmental Science & Technology. https://www.ijest.org/fasoracetam-treatment-adhd-a-systematic-review/. 
  14. ↑ 14.0 14.1 Poisons Standard February 2020. comlaw.gov.au



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