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Pharmacokinetic and behavioral effects of allopregnanolone in healthy women

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Abstract

Rationale

The behavioral effects of allopregnanolone (3α-hydroxy-5α-pregnan-20-one) in women are not known.

Objective

Allopregnanolone, a neuroactive steroid secreted by the mammalian ovary, exerts its anesthetic, anxiolytic, and sedative/hypnotic effects through potentiation of GABAA receptors. The purpose of this study was to evaluate the behavioral effects of allopregnanolone in healthy women.

Methods

Ten healthy women were given three increasing intravenous doses of allopregnanolone in the follicular phase of the menstrual cycle. Saccadic eye movement parameters and visual analogue scales of sedation were used to evaluate the behavioral response of allopregnanolone. Repeated blood samples for analyses of allopregnanolone were drawn throughout the study day.

Results

Exogenously administered allopregnanolone decreases saccadic eye movement parameters and increases subjective ratings of sedation that correlate with increased serum concentrations of this neuroactive steroid.

Conclusion

The behavioral effects of allopregnanolone are similar to that of its 5β-stereoisomer, pregnanolone (3α-hydroxy-5β-pregnan-20-one). Apart from fatigue and mild nausea, allopregnanolone given in a cumulative dose of 0.09 mg/kg did not have any adverse effects.

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Acknowledgements

This study was supported by grants from the Swedish Research Council, medicine proj. 4X-11198, EU structural fund objective 1 program, the Astrid Karlsson Foundation, and the Tore Nilsson Foundation.

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Authors and Affiliations

  1. Department of Clinical Science, Obstetrics and Gynecology, Umeå University, Umeå, Sweden

    Erika Timby, Sigrid Nyberg, Agneta Andersson, Di Zhu & Torbjörn Bäckström

  2. Hospital Pharmacy, University Hospital, Umeå, Sweden

    Matts Balgård

  3. Department of Clinical Pharmacology, Regional and University Hospital of Trondheim, Trondheim, Norway

    Olav Spigset

  4. AgriSera AB, Vännäs, Sweden

    Joanna Porankiewicz-Asplund

  5. Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA, USA

    Robert H. Purdy

  6. Department of Women's and Children's Health, University Hospital, Uppsala University, SE-751 85, Uppsala, Sweden

    Inger Sundström Poromaa

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  1. Erika Timby
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  2. Matts Balgård
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  3. Sigrid Nyberg
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  4. Olav Spigset
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  7. Robert H. Purdy
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  8. Di Zhu
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  9. Torbjörn Bäckström
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  10. Inger Sundström Poromaa
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Correspondence to Inger Sundström Poromaa.

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Timby, E., Balgård, M., Nyberg, S. et al. Pharmacokinetic and behavioral effects of allopregnanolone in healthy women. Psychopharmacology 186, 414–424 (2006). https://doi.org/10.1007/s00213-005-0148-7

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  • DOI: https://doi.org/10.1007/s00213-005-0148-7

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