Soporific Effect of the Neurosteroid Pregnanolone in Relation to the Substance’s Plasma Level: A Pilot Study

Abstract

The soporific effect of the neuroactive steroid pregnanolone, a metabolite of progesterone, and its relationship with plasma concentrations was assessed in 18 young, healthy, male volunteers for 2 h after administration of a single dose of pregnanolone prepared in two different formulations. Sedation was measured as sleep propensity and power increase in the low frequency delta band of the quantified EEG, based on 5-min polygraphic (EEG, EOG, EMG) recordings under resting conditions, which were performed immediately before, and 30, 60, 90, and 120 min after intake of the study drug. With both formulations, there was a time-dependent increase in plasma concentration of pregnanolone with highest values 1–2 h postdosing. The model of short polygraphic recordings under resting conditions demonstrated soporific effects of pregnanolone. Compared to predosing baseline the number of sleep attempts and the time asleep increased after treatment with a peak 60 min postdosing. Quantitative EEG analysis revealed an increase of absolute amplitude in the delta frequency range with a comparable temporal pattern. Correlations between the soporific effect and plasma concentrations of pregnanolone suggest that the effects were drug-related, although this has to be replicated with placebo control.

Ecdysteroid biosynthesis in workers of the European honeybee Apis mellifera L.

“…In mammalian brains, steroidogenic P450s are involved in the biosynthesis of locally acting neurosteroids (Mellon et al, 2001), which accumulate in the nervous system at levels much higher than those in the blood to modulate nervous function (Schumacher et al, 1996). In the adults, neurosteroids stimulate the sensitivity of neurotransmitter receptors, which affects animal behaviors associated with these receptors (Wieland et al, 1991;Fraile et al, 1988, Schulz et al, 1996. Neurosteroids are also involved in neuronal modeling such as embryonic axonal and Fig.…”

Acetaminophen does not affect 24-h body temperature or sleep in the luteal phase of the menstrual cycle

“…Progesterone and its metabolites enhance the effects of GABA (40) and may enhance SWS. Schulz et al (39) found an increase in amplitude in the delta frequency range of the EEG in young men after administration of pregnanolone, a neuroactive metabolite of progesterone. Moldofsky et al (30), however, found a decrease in SWS in the luteal phase compared with the follicular phase that correlated with plasma progesterone concentrations.…”

Insomnia related to postmenopausal syndrome and hormone replacement therapy: sleep laboratory studies on baseline differences between patients and controls and double‐blind, placebo‐controlled investigations on the effects of a novel estrogen–progestogen combination (Climodien®, Lafamme®) versus estrogen alone

“…While estrogen was found to enhance REM sleep (Schiff et al. , 1979), progesterone and its metabolite pregnanolone showed a marked sedating effect with a significant increase in NREM sleep (Schulz et al. , 1996).…”