Hedström Helena, Bixo Marie, Nyberg Sigrid, Spigset Olav, Zingmark Elisabeth, Bäckström Torbjörn
Umeå Neurosteroid Research Center, Department of Clinical Science, Obstetrics, and Gynecology, Umeå University, Umeå, Sweden.
Psychopharmacology (Berl). 2009 Mar;203(1):85-98. doi: 10.1007/s00213-008-1372-8. Epub 2008 Oct 24.
The pharmacokinetics and behavioral effects of isoallopregnanolone (3beta-hydoxy-5alpha-pregnan-20-one) in women are not known.
Allopregnanolone (3alpha-hydoxy-5alpha-pregnan-20-one) is a well-known neurosteroid, acting via the GABA(A) receptor in the human brain. The naturally occurring progesterone metabolite isoallopregnanolone is the 3beta-stereoisomer of allopregnanolone. Prior studies have concluded that isoallopregnanolone has no effect on the GABA(A) receptor. However, an antagonistic effect of isoallopregnanolone to allopregnanolone on the GABA(A) receptor has been shown in animal and in vitro studies. The purpose of this study was to evaluate the pharmacokinetics and behavioral effects of isoallopregnanolone in humans.
Six healthy women were given three increasing doses of isoallopregnanolone intravenously in the follicular phase. Repeated blood samples for analyses of isoallopregnanolone and allopregnanolone concentrations were drawn. Saccadic eye movement variables, self-rated sedation, and mood rating scales were used during the test day. A Likert scale for prospective symptoms was used to measure daily fluctuations during the ongoing menstrual cycle.
Exogenously administered isoallopregnanolone produced a dose-dependent increase in the serum concentration of isoallopregnanolone. In parallel, there was also a rise in the allopregnanolone concentration. There was a decrease in saccadic eye movement variables, but no effect was found on self-rated sedation or mood and no changes were seen in prospective symptoms during the menstrual cycle.
After administration of isoallopregnanolone at a cumulative dose of 0.20 mg/kg, no adverse effects were observed. There is a metabolism of isoallopregnanolone to allopregnanolone, most likely explaining the effects on the saccadic eye movements.
异别孕烷醇酮（3β-羟基-5α-孕烷-20-酮）在女性体内的药代动力学和行为效应尚不清楚。
别孕烷醇酮（3α-羟基-5α-孕烷-20-酮）是一种著名的神经甾体，通过人脑γ-氨基丁酸A（GABA(A)）受体发挥作用。天然存在的孕酮代谢产物异别孕烷醇酮是别孕烷醇酮的3β-立体异构体。先前的研究得出结论，异别孕烷醇酮对GABA(A)受体无作用。然而，在动物和体外研究中已显示异别孕烷醇酮对别孕烷醇酮在GABA(A)受体上具有拮抗作用。本研究的目的是评估异别孕烷醇酮在人体内的药代动力学和行为效应。
6名健康女性在卵泡期静脉注射递增剂量的异别孕烷醇酮。采集重复血样以分析异别孕烷醇酮和别孕烷醇酮浓度。在测试日使用眼跳运动变量、自评镇静和情绪评定量表。使用李克特量表评估预期症状，以测量月经周期中的每日波动。
外源性给予异别孕烷醇酮使血清异别孕烷醇酮浓度呈剂量依赖性增加。同时，别孕烷醇酮浓度也有所升高。眼跳运动变量减少，但自评镇静或情绪未受影响，月经周期中的预期症状也无变化。
累积剂量为0.20mg/kg的异别孕烷醇酮给药后未观察到不良反应。异别孕烷醇酮可代谢为别孕烷醇酮，这很可能解释了对眼跳运动的影响。
