Fasoracetam

Fasoracetam

Clinical data
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
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
IUPAC name (5R)-5-(piperidine-1-carbonyl)pyrrolidin-2-one
CAS Number	110958-19-5^Y
PubChem CID	198695
DrugBank	DB16163
ChemSpider	171980^Y
UNII	42O8UF5CJB
KEGG	C13311^Y
ChEBI	CHEBI:31592
ChEMBL	ChEMBL2106179^Y
CompTox Dashboard (EPA)	DTXSID9048855
Chemical and physical data
Formula	C10H16N2O2
Molar mass	196.250 g·mol^−1
3D model (JSmol)	Interactive image
SMILES C1CCN(CC1)C(=O)[C@H]2CCC(=O)N2
InChI 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^Y Key:GOWRRBABHQUJMX-MRVPVSSYSA-N^Y
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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

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 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

1. 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. 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. 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. 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. "Fasoracetam - Avalo Therapeutics". AdisInsight. Springer Nature Switzerland AG. 30 August 2021. Retrieved 1 October 2024.
6. "Fasoracetam - Nobias Therapeutics". AdisInsight. Springer Nature Switzerland AG. 17 October 2023. Retrieved 1 October 2024.
7. "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. Moskowitz DH (2017). Finding the Genetic Cause and Therapy for ADHD, Autism and 22q. BookBaby (self published). ISBN 9781483590981.
10. 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. 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. Poisons Standard February 2020. comlaw.gov.au