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  3. AV965 - Wikipedia
AV965 - Wikipedia
From Wikipedia, the free encyclopedia

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).[1][2] 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.[1][3]

Clinical development

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

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

Avera Pharmaceuticals is developing AV-965.[5] 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.[7]

See also

References

  1. ^ a b c Albert, 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. Retrieved 2025-05-29.
  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. Retrieved 2025-05-29.
  5. ^ a b "Avera Pharmaceutical". teaserclub.com. Retrieved 2025-05-29.
  6. ^ "Regulatory Requirements for the Clinical Development of New Therapies for the Treatment of Alzheimer's Disease" (PDF).
  7. ^ a b "The 5-HT1A receptor as a serotonergic target for neuroprotection in cerebral ischemia" (PDF).
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