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Isoallopregnanolone; an antagonist to the anaesthetic effect of allopregnanolone in male rats
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology. Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
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2005 (English)In: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 512, no 1, 15-21 p.Article in journal (Refereed) Published
Abstract [en]

The interaction of isoallopregnanolone (3β-OH-5α-pregnan-20-one) on allopregnanolone (3α-OH-5α-pregnan-20-one) induced anaesthesia was studied in male rats using burst suppression of 1 s (“silent second”) with an electroencephalographic-threshold method. The i.v. administration of isoallopregnanolone was varied in relation to induction of “silent second”. Pre-treatment with isoallopregnanolone (12.5–50 mg/kg iv) 2 min prior to the threshold test gave an increase in the threshold dose of allopregnanolone(ANOVA df(3;36), F=13.61, P<0.001), which was dose dependent (r=0.73, b [slope]=0.08, df=38, P<0.001). After isoallopregnanolone pre-treatment, but not in the controls, anaesthesia time was positively related to the dose of allopregnanolone (r=0.52, b=1.72, df=28,P<0.01). Anaesthesia times were not influenced by a corresponding administration of isoallopregnanolone immediately after induction of “silent second”. When allopregnanolone and isoallopregnanolone were infused together at molar ratios of 1:1, 1:1.23, 1:1.43, a linear increase of the threshold doses of allopregnanolone was seen in relation to the dose of isoallopregnanolone (r=0.86, b=0.40, df=8,P<0.01). Thus isoallopregnanolone can antagonise the anaesthetic action of allopregnanolone.

 

Place, publisher, year, edition, pages
Amsterdam: North-Holland , 2005. Vol. 512, no 1, 15-21 p.
Keyword [en]
Anesthetics/*antagonists & inhibitors/chemistry, Animals, Dose-Response Relationship; Drug, Electroencephalography, Male, Pregnanolone/*antagonists & inhibitors/chemistry/*pharmacology, Rats, Rats; Sprague-Dawley, Stereoisomerism
Identifiers
URN: urn:nbn:se:umu:diva-16936DOI: 10.1016/j.ejphar.2005.01.049PubMedID: 15814085OAI: oai:DiVA.org:umu-16936DiVA: diva2:156609
Available from: 2007-10-22 Created: 2007-10-22 Last updated: 2017-12-14Bibliographically approved

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Bäckström, TorbjörnWahlström, GöranWahlström, KerstinZhu, DiWang, Ming-De
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