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