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

Vol. 34, No. 2, 1996

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Pharmacoelectroencephalography

Soporific Effect of the Neurosteroid Pregnanolone in Relation to the Substance's Plasma Level: A Pilot Study
H. Schulz^a, M. Jobert^a, K.W. Gee^b, D.W. Ashbrook^c

^aPAREXEL GmbH, Independent Pharmaceutical Research Organization, Berlin, Germany;
^bDepartment of Pharmacology, College of Medicine, University of California, and
^cCoCensys Inc., Irvine, Calif, USA

Address of Corresponding Author

Neuropsychobiology 1996;34:106-112 (DOI: 10.1159/000119300)

Key Words

Pregnanolone
Sedation
EEG
Neuroactive steroid

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.

Author Contacts

Dr. Marc Jobert, PAREXEL GmbH, Klinikum Westend, Haus 18, Spandauer Damm 130, D-14050 Berlin (Germany)

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