Chemistry: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).[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
- ↑ 1.0 1.1 1.2 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. PMID 22826341.
- ↑ "Serotonin 5-HT1 Receptor Antagonists | DrugBank Online". https://go.drugbank.com/categories/DBCAT001739.
- ↑ Haddjeri, Nasser; Lavoie, Normand; Blier, Pierre (October 2004). "Electrophysiological Evidence for the Tonic Activation of 5-HT1A Autoreceptors in the Rat Dorsal Raphe Nucleus" (in en). Neuropsychopharmacology 29 (10): 1800–1806. doi:10.1038/sj.npp.1300489. ISSN 1740-634X. PMID 15127086. https://www.nature.com/articles/1300489.
- ↑ "BioWorld Science - Articles - Page 1608" (in en). https://www.bioworld.com/articles/topic/520-bioworld-science?page=1608,%20..
- ↑ 5.0 5.1 "Avera Pharmaceutical". https://teaserclub.com/investors/avera-pharmaceutical.
- ↑ "Regulatory Requirements for the Clinical Development of New Therapies for the Treatment of Alzheimer’s Disease". https://www.dgra.de/media/masterthesis/1246-master_vambrie_s.pdf.
- ↑ 7.0 7.1 "The 5-HT1A receptor as a serotonergic target for neuroprotection in cerebral ischemia". https://cris.maastrichtuniversity.nl/files/75345715/Prickaerts_2021_The_5_HT1A_receptor_as_a.pdf.
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