title: Isoallopregnanolone antagonize allopregnanolone-induced effects on saccadic eye velocity and self-reported sedation in humans.
abstract: Allopregnanolone (AP) is an endogenous neurosteroid. It modulates the effect of γ-amino-butyric acid (GABA) on the GABA type A (GABAA) receptor, which leads to increased receptor activity. Since the GABA-system is mainly inhibitory, increased AP activity leads to modulation of neuronal activity. In vitro studies of GABAA receptor activity and in vivo animal studies of sedation have shown that AP-induced effects can be inhibited by another endogenous steroid, namely isoallopregnanolone (ISO). In this study we investigated if ISO can antagonize AP-induced effects in healthy female volunteers, via measurements of saccadic eye velocity (SEV) and self-rated sedation. With a single-blind cross-over design, 12 women were studied on three separate occasions; given AP alone or AP in combination with one of two ISO doses. Congruent with previous reports, AP administration decreased SEV and induced sedation and these effects were diminished by simultaneous ISO administration. Also, the ISO effect modulation was seemingly stronger for SEV than for sedation. These effects were observed already at an ISO dose exposure that was approximately half of that of AP. In conclusion, ISO antagonized AP-induced decrease in SEV and self-reported sedation, probably in a non-competitive manner.
authors.affiliation: Umeå Neurosteroid Research Center, Department of Clinical Science, Umeå University, Umeå, Sweden.
authors.forename: Sara K S
authors.initials: SK
authors.lastname: Bengtsson
authors.affiliation: Umeå Neurosteroid Research Center, Department of Clinical Science, Umeå University, Umeå, Sweden.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Nyberg
authors.affiliation: Umeå Neurosteroid Research Center, Department of Clinical Science, Umeå University, Umeå, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Hedström
authors.affiliation: Umeå Neurosteroid Research Center, Department of Clinical Science, Umeå University, Umeå, Sweden.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Zingmark
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Jonsson
authors.affiliation: Umeå Neurosteroid Research Center, Department of Clinical Science, Umeå University, Umeå, Sweden. Electronic address: torbjorn.backstrom@obgyn.umu.se.
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Bäckström
authors.affiliation: Umeå Neurosteroid Research Center, Department of Clinical Science, Umeå University, Umeå, Sweden.
authors.forename: Marie
authors.initials: M
authors.lastname: Bixo
mesh_terms: D000328:Adult; D000777:Anesthetics / Q000097:blood / Q000494:pharmacology*; D016292:Procedural Sedation; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D011280:Pregnanolone / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000097:blood / Q000494:pharmacology*; D012438:Saccades / Q000187:drug effects*; D057566:Self Report; D016037:Single-Blind Method; D014851:Wakefulness / Q000187:drug effects*; D055815:Young Adult
chemical_list: D000777:Anesthetics; D011280:Pregnanolone
keywords: Allopregnanolone; GABA(A) receptor; Isoallopregnanolone; Premenstrual dysphoric disorder; Saccadic eye velocity; Sedation