AV965
AV-965 is a pharmacological compound being studied as a selective antagonist of the serotonin 5-HT1A receptor, with potential applications in neuropsychiatric disorders such as cognitive impairment and schizophrenia.
Mechanism of action
AV-965 acts by blocking the 5-HT1A receptor, a G protein-coupled receptor prevalent in the brain, especially in the raphe nuclei (where it acts as an autoreceptor) and in limbic and cortical regions (where it functions as a heteroreceptor).{{Cite journal |last=Albert |first=Paul R. |date=2012-09-05 |title=Transcriptional regulation of the 5-HT1A receptor: implications for mental illness |journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences |volume=367 |issue=1601 |pages=2402–2415 |doi=10.1098/rstb.2011.0376 |issn=1471-2970 |pmc=3405675 |pmid=22826341}}{{Cite web |title=Serotonin 5-HT1 Receptor Antagonists {{!}} DrugBank Online |url=https://go.drugbank.com/categories/DBCAT001739 |access-date=2025-05-29 |website=go.drugbank.com}} Antagonism of 5-HT1A autoreceptors can disinhibit serotonergic neuron firing, potentially enhancing serotonin release and improving cognitive and behavioral outcomes in conditions marked by reduced serotonergic tone.{{Cite journal |last1=Haddjeri |first1=Nasser |last2=Lavoie |first2=Normand |last3=Blier |first3=Pierre |date=October 2004 |title=Electrophysiological Evidence for the Tonic Activation of 5-HT1A Autoreceptors in the Rat Dorsal Raphe Nucleus |url=https://www.nature.com/articles/1300489 |journal=Neuropsychopharmacology |language=en |volume=29 |issue=10 |pages=1800–1806 |doi=10.1038/sj.npp.1300489 |pmid=15127086 |issn=1740-634X}}
Clinical development
AV-965 has entered early clinical trials, with Phase I studies in healthy volunteers demonstrating a favorable safety and tolerability profile.{{Cite web |title=BioWorld Science - Articles - Page 1608 |url=https://www.bioworld.com/articles/topic/520-bioworld-science?page=1608,%20. |access-date=2025-05-29 |website=www.bioworld.com |language=en}}
Potential therapeutic indications
The compound is under investigation for the treatment of cognitive impairment, particularly in schizophrenia and possibly Alzheimer’s disease.{{Cite web |title=Avera Pharmaceutical |url=https://teaserclub.com/investors/avera-pharmaceutical |access-date=2025-05-29 |website=teaserclub.com}}https://www.dgra.de/media/masterthesis/1246-master_vambrie_s.pdf {{Bare URL PDF|date=June 2025}} The rationale for targeting the 5-HT1A receptor is supported by research showing its influence on cognition, mood, and anxiety.https://cris.maastrichtuniversity.nl/files/75345715/Prickaerts_2021_The_5_HT1A_receptor_as_a.pdf {{Bare URL PDF|date=June 2025}}
Current research
Avera Pharmaceuticals is developing AV-965. Selective 5-HT1A receptor modulation is a promising strategy in neuropsychiatric drug development, as both agonists and antagonists have shown potential in preclinical models for improving cognitive and behavioral symptoms.