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Pharmacokinetic and behavioral effects of allopregnanolone in healthy women.

Posted by on in 2006
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Timby E, Balgård M, Nyberg S, Spigset O, Andersson A, Porankiewicz-Asplund J, Purdy RH, Zhu D, Bäckström T, Poromaa IS.
Psychopharmacology (Berl). 2006 Jun;186(3):414-24. Epub 2005 Sep 21.
Department of Clinical Science, Obstetrics and Gynecology, Umeå University, and Hospital Pharmacy, University Hospital, Umeå, Sweden.

RATIONALE: The behavioral effects of allopregnanolone (3alpha-hydroxy-5alpha-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 5beta-stereoisomer, pregnanolone (3alpha-hydroxy-5beta-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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