Caffeine and sclareol reduce the sedative effects of linalool, possibly through the GABA A interaction pathway: molecular insights through in vivo and in silico studies

Abstract Study background: Linalool (LIN) has some important neuropharmacological activities, including anxiolytic and sedative effects. It is also clear that it protects experimental animals from convulsions and Alzheimer's disease. On the other hand, caffeine (CAF) and sclareol (SCL) have neurostimulatory potential. Aim To evaluate the sedative effect and possible molecular mechanisms of CAF with LIN and/or SCL through in vivo and in silico studies. Methodology: CAF (10 mg/kg) alone or with LIN (50 mg/kg) and/or SCL (10 mg/kg) were intraperitoneally (i.p.) treated before thirty minutes of pentobarbital sodium (TS) injection (40 mg/kg, i.p.) to the mice and observed for latency and duration of sleep up to 4 hours. To understand the possible action mechanisms of these drugs, we also performed molecular docking studies with GABAA receptor respective submits. Results Findings suggest that LIN exerted significant (p A receptor (α1 and β2 subunits), respectively. Conclusion LIN exerted significant sedative effects, while CAF and/or SCL reduced this effect in animals. We suppose these drugs may exert their sedative effects through the GABAA receptor intrecation pathway. Further studies are required to confirm these results.