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Zingmark, Elisabeth
Publications (6 of 6) Show all publications
Bengtsson, S. K. S., Nyberg, S., Hedström, H., Zingmark, E., Jonsson, B., Bäckström, T. & Bixo, M. (2015). Isoallopregnanolone antagonize allopregnanolone-induced effects on saccadic eye velocity and self-reported sedation in humans. Psychoneuroendocrinology, 52, 22-31.
Open this publication in new window or tab >>Isoallopregnanolone antagonize allopregnanolone-induced effects on saccadic eye velocity and self-reported sedation in humans
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2015 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 52, 22-31 p.Article in journal (Refereed) Published
Abstract [en]

Allopregnanolone (AP) is an endogenous neurosteroid. It modulates the effect of gamma-amino-butyric acid (GABA) on the GABA type A (GABA(A)) 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 GABA(A) 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.

Keyword
Allopregnanolone, Isoallopregnanolone, Saccadic eye velocity, GABA(A) receptor, Sedation, Premenstrual dysphoric disorder
National Category
Endocrinology and Diabetes Neurosciences
Identifiers
urn:nbn:se:umu:diva-100765 (URN)10.1016/j.psyneuen.2014.10.025 (DOI)000349271000004 ()25459890 (PubMedID)
Available from: 2015-04-26 Created: 2015-03-09 Last updated: 2018-01-11Bibliographically approved
Hedström, H., Bixo, M., Nyberg, S., Spigset, O., Zingmark, E. & Bäckström, T. (2009). Studies of pharmacokinetic and pharmacodynamic properties of isoallopregnanolone in healthy women. Psychopharmacology, 203(1), 85-98.
Open this publication in new window or tab >>Studies of pharmacokinetic and pharmacodynamic properties of isoallopregnanolone in healthy women
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2009 (English)In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 203, no 1, 85-98 p.Article in journal (Refereed) Published
Abstract [en]

Rationale  The pharmacokinetics and behavioral effects of isoallopregnanolone (3β-hydoxy-5α-pregnan-20-one) in women are not known. Objectives  Allopregnanolone (3α-hydoxy-5α-pregnan-20-one) is a well-known neurosteroid, acting via the GABAA receptor in the human brain. The naturally occurring progesterone metabolite isoallopregnanolone is the 3β-stereoisomer of allopregnanolone. Prior studies have concluded that isoallopregnanolone has no effect on the GABAA receptor. However, an antagonistic effect of isoallopregnanolone to allopregnanolone on the GABAA 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.

Materials and methods  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.

Results  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.

Conclusions  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.

Keyword
Isoallopregnanolone, Neurosteroids, Pharmacokinetics, Pharmacodynamics, Women
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:umu:diva-49365 (URN)10.1007/s00213-008-1372-8 (DOI)
Available from: 2011-11-10 Created: 2011-11-10 Last updated: 2017-12-08Bibliographically approved
Nyberg, S., Bäckström, T., Zingmark, E., Purdy, R. H. & Poromaa, I. S. (2007). Allopregnanolone decrease with symptom improvement during placebo and gonadotropin-releasing hormone agonist treatment in women with severe premenstrual syndrome. Gynecological Endocrinology, 23(5), 257-266.
Open this publication in new window or tab >>Allopregnanolone decrease with symptom improvement during placebo and gonadotropin-releasing hormone agonist treatment in women with severe premenstrual syndrome
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2007 (English)In: Gynecological Endocrinology, ISSN 0951-3590, E-ISSN 1473-0766, Vol. 23, no 5, 257-266 p.Article in journal (Refereed) Published
Keyword
Adult, Buserelin/administration & dosage/*therapeutic use, Cross-Over Studies, Double-Blind Method, Female, Fertility Agents; Female/administration & dosage/*therapeutic use, Humans, Luteal Phase/blood, Placebo Effect, Pregnanolone/*blood, Premenstrual Syndrome/blood/*drug therapy, Progesterone/*blood, Treatment Outcome
Identifiers
urn:nbn:se:umu:diva-16912 (URN)10.1080/09513590701253511 (DOI)17558683 (PubMedID)
Available from: 2007-10-19 Created: 2007-10-19 Last updated: 2017-12-14Bibliographically approved
Nyberg, S., Andersson, A., Zingmark, E., Wahlström, G., Bäckström, T. & Sundström-Poromaa, I. (2005). The effect of a low dose of alcohol on allopregnanolone serum concentrations across the menstrual cycle in women with severe premenstrual syndrome and controls.. Psychoneuroendocrinology, 30(9), 892-901.
Open this publication in new window or tab >>The effect of a low dose of alcohol on allopregnanolone serum concentrations across the menstrual cycle in women with severe premenstrual syndrome and controls.
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2005 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 30, no 9, 892-901 p.Article in journal (Refereed) Published
Keyword
Adult, Analysis of Variance, Ethanol/administration & dosage/*blood, Female, Follicular Phase/*blood/drug effects, Humans, Hydrocortisone/*blood, Infusions; Intravenous, Luteal Phase/*blood/drug effects, Middle Aged, Pregnanolone/*blood, Premenstrual Syndrome/*blood/diagnosis, Reference Values, Severity of Illness Index, Statistics; Nonparametric
Identifiers
urn:nbn:se:umu:diva-16934 (URN)10.1016/j.psyneuen.2005.04.016 (DOI)15979810 (PubMedID)
Available from: 2007-10-22 Created: 2007-10-22 Last updated: 2017-12-14Bibliographically approved
Turkmen, S., Lundgren, P., Birzniece, V., Zingmark, E., Bäckström, T. & Johansson, I.-M. (2004). 3beta-20beta-dihydroxy-5alpha-pregnane (UC1011) antagonism of the GABA potentiation and the learning impairment induced in rats by allopregnanolone.. European Journal of Neuroscience, 20(6), 1604-1612.
Open this publication in new window or tab >>3beta-20beta-dihydroxy-5alpha-pregnane (UC1011) antagonism of the GABA potentiation and the learning impairment induced in rats by allopregnanolone.
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2004 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 20, no 6, 1604-1612 p.Article in journal (Refereed) Published
Abstract [en]

Allopregnanolone is a progesterone metabolite and GABA-A receptor modulator with benzodiazepine like effects, including decreased learning and memory. In vitro 3beta-hydroxypregnane steroids antagonize allopregnanolone-induced effects, but no antagonism has been shown in vivo. Our purpose was to evaluate 3beta-20beta-dihydroxy-5alpha-pregnane (UC1011) as a blocker of allopregnanolone-induced effects in vivo and in vitro in rats. We tested adult male Wistar rats in the Morris water maze 8 min after daily injections (i.v.) of allopregnanolone 2 mg/kg (n = 21); allopregnanolone : UC1011 2 : 6 (n = 7), 2 : 8 (n = 7), 2 : 20 (n = 14) mg/kg; UC1011 20 mg/kg (n = 14); or vehicle (10% 2-hydroxypropyl-beta-cyclodextrin, n = 4). Studies of chloride ion uptake into cortical and hippocampal membrane preparations were performed. The latency to find the hidden platform was still high in the allopregnanolone-injected group on day 6. Day 3-6 rats injected with allopregnanolone and UC1011 (2 : 20 mg/kg) had lower latency (P < 0.05), compared to the allopregnanolone-injected group. The group that only received UC1011 learned the location of the platform as fast as the controls. There was no significant difference in swim speed between groups. The time spent swimming close to the pool wall was in the allopregnanolone : UC1011 group (2 : 20 mg/kg) significantly decreased (P < 0.05, day 3-6), compared to the allopregnanolone-injected group. The increased chloride ion uptake induced by increasing dosage of allopregnanolone in the presence of 10 micro m GABA was significantly decreased with UC1011 (P < 0.01), in both cortical and hippocampal homogenates. In conclusion, UC1011 can via antagonism at the GABA-A receptor reduce the negative allopregnanolone effect on learning in the water maze.

Keyword
Analysis of Variance, Animals, Behavior; Animal, Cerebral Cortex/drug effects/metabolism, Chlorides/metabolism, Chromatography; High Pressure Liquid/methods, Dose-Response Relationship; Drug, Drug Synergism, GABA Antagonists/*therapeutic use, GABA Modulators/blood/*toxicity, Hippocampus/drug effects/metabolism, Learning Disorders/chemically induced/*drug therapy, Male, Maze Learning/drug effects, Pregnanediol/pharmacology/*therapeutic use, Pregnanolone/blood/pharmacology/therapeutic use/*toxicity, Radioimmunoassay/methods, Rats, Rats; Wistar, Reaction Time/drug effects, Statistics; Nonparametric, Time Factors, gamma-Aminobutyric Acid/physiology
Identifiers
urn:nbn:se:umu:diva-16941 (URN)10.1111/j.1460-9568.2004.03610.x (DOI)15355327 (PubMedID)
Available from: 2007-10-22 Created: 2007-10-22 Last updated: 2017-12-14Bibliographically approved
Bäckström, T., Andersson, A., Andreén, L., Birzniece, V., Bixo, M., Björn, I., . . . Zingmark, E. (2003). Pathogenesis in menstrual cycle-linked CNS disorders.. Annals of the New York Academy of Sciences, 1007, 42-53.
Open this publication in new window or tab >>Pathogenesis in menstrual cycle-linked CNS disorders.
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2003 (English)In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 1007, 42-53 p.Article, review/survey (Other academic) Published
Keyword
Affect/physiology, Animals, Female, Humans, Menstrual Cycle/*physiology, Mood Disorders/*etiology/physiopathology/psychology, Pregnanolone/physiology, Premenstrual Syndrome/*etiology/physiopathology/psychology, Receptors; GABA-A/physiology
Identifiers
urn:nbn:se:umu:diva-16450 (URN)10.1196/annals.1286.005 (DOI)14993039 (PubMedID)
Available from: 2007-09-28 Created: 2007-09-28 Last updated: 2017-12-14Bibliographically approved
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