Fasoracetam
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| Other names | AEVI-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 |
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| Pharmacokinetic data | |
| Bioavailability | 79–97% (animals)[1] |
| Elimination half-life | 4–6.5 hours[1] |
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| Chemical and physical data | |
| Formula | C10H16N2O2 |
| Molar mass | 196.250 g·mol−1 |
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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
[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]- ^ a b c d e f g Malykh, AG; Sadaie, MR (12 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.
- ^ a b 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". Curr Pharm Des. 8 (2): 125–138. doi:10.2174/1381612023396582. PMID 11812254.
- ^ a b c d e f g h i j k l Connolly, J; Glessner, J; Kao, C; Elia, J; Hakonarson, H (2015). "ADHD & Pharmacotherapy: Past, Present and Future: A Review of the Changing Landscape of Drug Therapy for Attention Deficit Hyperactivity Disorder". Ther Innov Regul Sci. 49 (5): 632–642. doi:10.1177/2168479015599811. PMC 4564067. PMID 26366330.
- ^ a b 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.
- ^ a b c d "Fasoracetam - Avalo Therapeutics". AdisInsight. 30 August 2021. Retrieved 1 October 2024.
- ^ a b c d "Fasoracetam - Nobias Therapeutics". AdisInsight. 17 October 2023. Retrieved 1 October 2024.
- ^ a b c d "Co-crystallised fasoracetam - Avalo Therapeutics". AdisInsight. 28 April 2023. Retrieved 1 October 2024.
- ^ "Recommended INN List 40" (PDF). WHO Drug Information. 12 (2). 1998.
- ^ a b Moskowitz, D. H. (2017). Finding the Genetic Cause and Therapy for ADHD, Autism and 22q. BookBaby (self published). ISBN 9781483590981.
- ^ a b c Sharma, B. (7 October 2016). "Medgenics: NFC-1 Could Be A Key Future Revenue Driver". Seeking Alpha.
- ^ "Press Release: Medgenics, Inc. Announces Name Change to Aevi Genomic Medicine, Inc". Aevi via MarketWired. 16 December 2016.
- ^ a b Elia, Josephine; Ungal, Grace; Kao, Charlly; Ambrosini, Alexander; De Jesus-Rosario, Nilsa; Larsen, Lene; Chiavacci, Rosetta; Wang, Tiancheng; Kurian, Christine; Titchen, Kanani; Sykes, Brian (2018-01-16). "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. ISSN 2041-1723. PMC 5770454. PMID 29339723.
- ^ Tardner, P (2020-09-09). "Fasoracetam as a treatment for ADHD: A systematic review of available clinical data". International Journal of Environmental Science & Technology.
- ^ a b Poisons Standard February 2020. comlaw.gov.au