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AV965

From Wikipedia, the free encyclopedia

AV-965 is a pharmacological compound being studied as a selectiveantagonist of the serotonin5-HT1A receptor, with potential applications inneuropsychiatric disorders such ascognitive impairment andschizophrenia.

Mechanism of action

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AV-965 acts by blocking the 5-HT1A receptor, aG protein-coupled receptor prevalent in the brain, especially in theraphe nuclei (where it acts as an autoreceptor) and inlimbic andcortical regions (where it functions as a heteroreceptor).[1][2] Antagonism of 5-HT1Aautoreceptors can disinhibitserotonergic neuron firing, potentially enhancingserotonin release and improving cognitive and behavioral outcomes in conditions marked by reducedserotonergic tone.[1][3]

Clinical development

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AV-965 has entered early clinical trials, with Phase I studies in healthy volunteers demonstrating a favorable safety and tolerability profile.[4]

Potential therapeutic indications

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The compound is under investigation for the treatment of cognitive impairment, particularly in schizophrenia and possibly Alzheimer’s disease.[5][6] The rationale for targeting the 5-HT1A receptor is supported by research showing its influence on cognition, mood, and anxiety.[1][7]

Current research

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Avera Pharmaceuticals is developing AV-965.[5] Selective 5-HT1A receptor modulation is a promising strategy in neuropsychiatric drug development, as bothagonists and antagonists have shown potential in preclinical models for improving cognitive and behavioral symptoms.[7]

See also

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References

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  1. ^abcAlbert, Paul R. (2012-09-05)."Transcriptional regulation of the 5-HT1A receptor: implications for mental illness".Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences.367 (1601):2402–2415.doi:10.1098/rstb.2011.0376.ISSN 1471-2970.PMC 3405675.PMID 22826341.
  2. ^"Serotonin 5-HT1 Receptor Antagonists | DrugBank Online".go.drugbank.com. Retrieved2025-05-29.
  3. ^Haddjeri, Nasser; Lavoie, Normand; Blier, Pierre (October 2004)."Electrophysiological Evidence for the Tonic Activation of 5-HT1A Autoreceptors in the Rat Dorsal Raphe Nucleus".Neuropsychopharmacology.29 (10):1800–1806.doi:10.1038/sj.npp.1300489.ISSN 1740-634X.PMID 15127086.
  4. ^"BioWorld Science - Articles - Page 1608".www.bioworld.com. Retrieved2025-05-29.
  5. ^ab"Avera Pharmaceutical".teaserclub.com. Retrieved2025-05-29.
  6. ^"Regulatory Requirements for the Clinical Development of New Therapies for the Treatment of Alzheimer's Disease"(PDF).
  7. ^ab"The 5-HT1A receptor as a serotonergic target for neuroprotection in cerebral ischemia"(PDF).
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