Dual Molecules Targeting 5-HT₆ and GABA-A Receptors as a New Approach to Combat Depression Associated with Neuroinflammation.

ABSTRACT: While monoaminergic deficits are evident in all depressed patients, nonresponders are characterized by impaired GABA-ergic signaling and the simultaneous presence of the inflammatory component. Pharmacological agents able to curb pathological immune responses and modulate ineffective GABA-ergic neurotransmission are thought to improve therapeutic outcomes in the treatment-resistant subgroup of depressed patients. Here, we report on a set of dually acting molecules designed to simultaneously modulate GABA-A and 5-HT₆ receptor activity. The serotonin 5-HT₆ receptor was chosen as a complementary molecular target, due to its promising antidepressant-like activities reported in animal studies. Within the study we identified that lead molecule 16 showed a desirable r

SUBMITTER: Marcinkowska M 

PROVIDER: S-EPMC10119930 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature