Diazepam

Contrary to its widespread use as a positive control in anxiety research, diazepam (0.5, 1, or 2 mg/kg i.p.) showed no anxiolytic effect in male or female C57BL/6J mice tested on the elevated plus maze, even after restraint stress. The highest dose (2 mg/kg) impaired locomotor activity, likely due to sedation. In contrast, the SSRI paroxetine (10 mg/kg) significantly reduced anxiety‑like behavior without sedation. The authors caution that diazepam may not be a reliable positive control in mouse preclinical anxiety screening and suggest re‑evaluating its use.

Fig. 1 Lack of anxiolytic effect of diazepam in the elevated plus maze. (Pádua-Reis M, et al., 2021)

Post hoc analysis of 4466 treated seizure clusters (3225 evaluable) from a 1‑year safety study of diazepam nasal spray in refractory epilepsy patients. Median times from seizure start to dose, dose to termination, and total duration were 2, 3, and 7 minutes overall. When treated in <5 minutes (median 1 min), median dose‑to‑termination was 2 min and total duration 4 min. When treated ≥5 minutes (median 10 min), dose‑to‑termination was 10 min and total duration 23 min. Early administration dramatically shortens seizure duration, echoing status epilepticus guidelines.

Fig. 2 Data preparation for treated seizure observations used in temporal analysis. (Misra SN, et al., 2024)