Isoallopregnanolone; an antagonist to the anaesthetic effect of allopregnanolone in male rats
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
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.
Anesthetics/*antagonists & inhibitors/chemistry, Animals, Dose-Response Relationship; Drug, Electroencephalography, Male, Pregnanolone/*antagonists & inhibitors/chemistry/*pharmacology, Rats, Rats; Sprague-Dawley, Stereoisomerism
IdentifiersURN: urn:nbn:se:umu:diva-16936DOI: 10.1016/j.ejphar.2005.01.049PubMedID: 15814085OAI: oai:DiVA.org:umu-16936DiVA: diva2:156609