| Popis: |
The novel synthetic neuroactive steroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH) blocks T-type calcium channels but does not directly modulate neuronal γ-aminobutyric acid type A (GABAWe used a combination of behavioural loss of righting reflex, neuroendocrine, pharmacokinetic, in vitro patch-clamp electrophysiology, and in vivo electrophysiological approaches in wild-type mice and in genetic knockouts of the CaAdult male mice were less sensitive to the hypnotic effects of 3β-OH compared with female mice, and these differences appeared during development. Adult males had higher 3β-OH brain concentrations despite being less sensitive to its hypnotic effects. Females metabolised 3β-OH into the active GABAThe sex-specific differences in the hypnotic effect of 3β-OH in mice are attributable to differences in its peripheral metabolism into the more potent hypnotic metabolite 3α-OH. |
