Sedative Potential of L (+)-Tartaric Acid: Behavioral Evidence With In Silico Insights Into Possible GABAergic...

Insomnia is a prevalent neurological disorder often caused by stress, anxiety, and imbalances in the GABAergic system. Although benzodiazepines like diazepam (DZP) are commonly prescribed, their long-term use is associated with adverse effects, including dependence and impaired coordination. Therefore, there is growing interest in natural alternatives with safer pharmacological profiles.

This study aimed to investigate the sedative-like potential of L (+)-tartaric acid (LTA), a naturally occurring organic acid, through both in vivo and in silico approaches targeting the γ-aminobutyric acid A (GABA_A) receptor. Sedative-like activity was evaluated in Swiss albino mice using thiopental sodium-induced sleeping time, open-field, and rotarod tests.

LTA significantly reduced sleep latency and prolonged sleep duration in a dose-dependent manner, with the higher dose (240 mg/kg) producing a more pronounced effect. Co-administration of LTA with DZP further enhanced thiopental-induced hypnosis. In the open-field test, LTA reduced locomotor and exploratory activities, as evidenced by decreases in square crossings, rearing, and grooming behaviors. Rotarod assessment demonstrated a dose-dependent reduction in motor coordination and neuromuscular performance, although the impairment remained less pronounced than that produced by DZP at the lower tested dose. Molecular docking revealed lower binding affinity than DZP but demonstrated multiple hydrogen-bond (HB) interactions with key amino acid (AA) residues of the GABA_A receptor, suggesting a potentially stable receptor interaction.

Collectively, the behavioral and computational findings indicate that LTA possesses sedative-like properties and may modulate GABAergic neurotransmission. Further mechanistic, pharmacokinetic, and electrophysiological studies are required to clarify its precise mode of action and therapeutic potential.