Fasoracetam

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| _other_data=(5R)-5-(piperidine-1-carbonyl)pyrrolidin-2-one

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Fasoracetam (Template:Abbrlink) is an experimental drug of the racetam group which was never marketed.<ref name="Malykh2010">Template:Cite journal</ref><ref name="GualtieriManettiRomanelli2002">Template:Cite journal</ref><ref name="ConnollyGlessnerKao2015">Template:Cite journal</ref> It is a putative nootropic that failed to show sufficient efficacy in clinical trials for vascular dementia.<ref name="ConnollyGlessnerKao2015" /> 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<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>Template:Cite journal</ref> In any case, it remains under development for treatment of DiGeorge syndrome.<ref name="AdisInsight-Nobias" />

Pharmacology

Fasoracetam appears to modulate and stimulate all three groups of metabotropic glutamate receptors (mGluRs).<ref name="ConnollyGlessnerKao2015" /><ref name="Malykh2010" /> It has been found to improve certain aspects of cognitive function in rodent studies.<ref name="ConnollyGlessnerKao2015" /><ref name="Malykh2010" /> The drug is orally bioavailable and is excreted mostly unchanged in urine.<ref name="Malykh2010" /><ref name="ConnollyGlessnerKao2015" />

Chemistry

Fasoracetam is a racetam and a derivative of pyroglutamic acid.<ref name="Malykh2010" /><ref name="GualtieriManettiRomanelli2002" />

History

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 Phase 3 clinical trials for vascular dementia, and abandoned it due to lack of efficacy.<ref name="ConnollyGlessnerKao2015" /><ref name="Hoskowitz2017">Template:Cite book</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>Template:Cite web</ref>

Clinical trials in adolescents with ADHD who also have mGluR mutations started in 2016.<ref name="SeekingAlpha2016">Template:Cite news</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>Template:Cite journal</ref> Studies showing improvements in cognitive function from fasoracetam have exclusively been done on rodents.<ref name="pmid29339723">Template:Cite journal</ref>

Society and culture

Legality

Australia

Fasoracetam is a schedule 4 substance in Australia under the Poisons Standard (February 2020).<ref name="PoisonsStandard2020">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 phase 3 clinical trials 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 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.<ref name="AdisInsight-Avalo">Template:Cite web</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 phase 2 clinical trials for this use as of October 2023.<ref name="AdisInsight-Nobias">Template:Cite web</ref> 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.<ref name="AdisInsight-Avalo-Co-Crystal">Template:Cite web</ref> However, no recent development has been reported for these indications as of April 2023.<ref name="AdisInsight-Avalo-Co-Crystal" />

The results of clinical studies for ADHD with fasoracetam have not shown statistical significance in efficacy.<ref name="NageyeCortese2019">Template:Cite journal</ref>