Anaesthetic effects of pregnanolone in combination with allopregnanolone, thiopental, hexobarbital and flurazepam: an EEG study in the rat.

Abstract

The anaesthetic interactions of the steroid, 3 alpha-hydroxy-5 beta-pregnan-20-one, in male rats were investigated in different fixed binary combinations with the steroid allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one), two barbiturates (thiopental and hexobarbital) and the benzodiazepine, flurazepam. Anaesthetic effects were determined using an EEG threshold method. Interactions were assessed using an isobolographic method. The interaction between the two steroids, pregnanolone and allopregnanolone, showed an anaesthetic effect significantly less than additive (antagonistic). The interactions between pregnanolone and the two barbiturates and the benzodiazepine showed an anaesthetic effect significantly greater than additive (potentiation) in all tests performed. These results could be explained by a pharmacodynamic interaction at the hypothetical GABA-benzodiazepine-barbiturate-steroid complex in the CNS.