Effect of remimazolam toluene sulfonate on the cognitive function of juveniles and its mechanism of action

Remimazolam is a new benzodiazepine. Currently, it remains unclear how repeated exposure to remimazolam affects the cognitive function of the developing brain. In the present study, the equivalent doses of the two sedatives were derived from S-shaped dose-response curves, and the ED95 of remimazolam was 45 mg/kg (95% CI 37.579-79.280), and for midazolam, it was 77 mg/kg (95% CI 63.751-127.21) using probability analysis. Then, we evaluated the effects of remimazolam and midazolam on cognitive function in juvenile mice (C57BL/6) through Y-maze and MWM. TUNEL staining was used to observe the apoptosis of neurons in hippocampus, western blotting was used to detect the expression changes of related proteins, and the changes of LTP were observed by recording the activity of neurons through electrical stimulation. We found that there was no significant difference in the behavior of mice in MWM. However, the short-term memory of developing mice was impaired in Y-maze after repeated exposure to remimazolam and midazolam. Furthermore, our data demonstrated that the short-term memory damage caused by remimazolam is lighter than midazolam. Concurrently, the extent of caspase-3 upregulation, the number of neuronal apoptosis in CA1 and CA3 regions, a downward trend of PSD95 and BDNF in the hippocampus, and the inhibition of LTP were highly consistent with the behavior of short-term memory impairment. These results indicate that the degree of memory impairment caused by remimazolam is milder than that caused by midazolam, making it a potential replacement for midazolam in repeated medication and long-term sedation in children.