Sedative potential of palmatine chloride in thiopental sodium-induced chicks: evidence from in vivo and in Silico studies

The aim of this study is to assess the sedative impact of palmatine chloride (PME) in thiopental sodium-induced sleeping chicks and its underlying molecular mechanism by using in vivo and in silico approaches. Chicks received PME per orally (p.o.) at doses of 1.25, 2.5, and 5 mg/kg per body weight (b.w.), while diazepam (DZP) (2 mg/kg) served as a positive control and vehicle as a negative control. For the purpose of evaluating the experimental compounds synergistic or antagonistic effects, a combination of PME and DZP was administered to the chicks. After thirty minutes, thiopental sodium (40 mg/kg, intraperitoneal (i.p.)) was administered to induce sleep, and latency to sleep onset and sleep duration were measured. In vivo results showed that PME reduced sleep latency and prolonged sleep duration in a dose-dependent manner, with the combination therapy producing a significant enhancement of these effects. In silico docking revealed PME binding to gamma-aminobutyric acid A (GABA_A) receptor α1 and β2 subunits (-7.2 kcal/mol) with shared amino acids. Pharmacokinetic and toxicity analyses suggested favorable drug-like properties. These results indicate PME's sedative potential, alone or with DZP, likely via GABAergic modulation, warranting further functional validation.