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British Journal of Anaesthesia, 2001, Vol. 86, No. 3 403-412
© 2001 The Board of Management and Trustees of the British Journal of Anaesthesia

Research

Evaluation and comparison of the pharmacokinetic and pharmacodynamic properties of allopregnanolone and pregnanolone at induction of anaesthesia in the male rat

D. Zhu1, M. D. Wang1, T. Bäckström1 and G. Wahlström2

1Department of Clinical Science, Section of Obstetrics and Gynaecology, University of Umeå, S-901 87 Umeå, Sweden. 2Department of Pharmacology and Clinical Neuroscience, University of Umeå, S-901 87 Umeå, Sweden*Corresponding author

Abstract

We have evaluated and compared the pharmacokinetic and pharmacodynamic properties of allopregnanolone and pregnanolone at induction of anaesthesia in male rats. A threshold method was used, and the first burst suppression period of 1 s or more in the EEG was selected as the end-point after fairly slow infusions. An optimal dose of 4.0 mg kg–1 min–1 was noted for both steroids. Brain concentrations were low at low infusion rates, indicating that acute tolerance was not occurring. Significant positive correlations were noted between dose rate and serum concentrations of allopregnanolone (r = 0.94, P<0.001) and pregnanolone (r = 0.88, P<0.001). Such correlations were also seen in striatum, cerebellum, cortex and muscle for both steroids (P<0.01). Despite changing infusion rates, the concentrations of both steroids in brainstem, hippocampus and fat remained stable. Because no correlation between infusion rate and steroid concentration was noted in the brainstem and hippocampus, these two brain areas may be regarded as primary sites of action for allopregnanolone and pregnanolone. Pregnanolone concentrations in the brainstem and hippocampus were significantly higher than those of allopregnanolone, suggesting that allopregnanolone was more potent than pregnanolone in inducing anaesthesia.

Br J Anaesth 2001; 86: 403–12


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Home page
 Br J AnaesthHome page
D. Zhu, V. Birzniece, T. Backstrom, and G. Wahlstrom
Dynamic aspects of acute tolerance to allopregnanolone evaluated using anaesthesia threshold in male rats
Br. J. Anaesth., October 1, 2004; 93(4): 560 - 567.
[Abstract] [Full Text] [PDF]


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