Evaluation of the procognitive activity of HBK-10, 5-HT_1A and D₂ antagonist with antidepressant-like properties

The idea

Despite major advances in antidepressant therapy, cognitive dysfunction remains largely unaddressed - even though it strongly predicts long-term recovery and everyday functioning. This project set out to explore whether targeting specific serotonin and dopamine receptors could produce antidepressant effects while also improving cognition.

Our approach

We investigated HBK-10, a methoxyphenylpiperazine derivative acting as a 5-HT_1A and D₂ receptor antagonist. Its procognitive potential was evaluated in a behavioral model of memory deficits resulting from glutamatergic hypofunction. To uncover underlying mechanisms, we examined the expression and phosphorylation of proteins associated with synaptic plasticity and memory consolidation. Together, these behavioral and molecular findings provided insight into how HBK-10 may support cognitive performance.

Why it matters

Cognitive dysfunction often persists even after mood symptoms subside. By targeting both mood and cognition, HBK-10 represents a promising step toward next-generation antidepressants that promote full functional recovery.

Grant number: 2025/09/X/NZ7/00286