Isoallopregnanolone; an antagonist to the anaesthetic effect of allopregnanolone in male rats.
The interaction of isoallopregnanolone (3 beta-OH-5 alpha-pregnan-20-one) on allopregnanolone (3 alpha-OH-5 alpha-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.
Bäckström
Torbjörn
T
Umeå Neurosteroid Research Center, Department of Clinical Science, Obstetrics and Gynaecology, Norrlands University Hospital, Umeå University, Umeå, Sweden. Torbjorn.Backstrom@Obgyn.umu.se
Wahlström
Göran
G
Wahlström
Kerstin
K
Zhu
Di
D
Wang
Ming-De
MD
D000777:Anesthetics / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D008297:Male; D011280:Pregnanolone / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D000777:Anesthetics; D011280:Pregnanolone