The anaesthetic potency of 3 alpha-hydroxy-5 alpha-pregnan-20-one and 3 alpha-hydroxy-5 beta-pregnan-20-one determined with an intravenous EEG-threshold method in male rats.

Two progesterone metabolites 3 alpha-hydroxy-5 alpha-pregnan-20-one (5-alpha) and 3 alpha-hydroxy-5 beta-pregnan-20-one (5-beta) were investigated for anaesthetic potency in male rats with an EEG-threshold method. Dose rate curves were obtained by infusing 5-alpha and 5 beta intravenously with different rates until an EEG-criterion (a burst suppression of one sec. or more, the "silent second") was seen in the EEG. The potency of the investigated drugs has been estimated by comparing threshold doses at optimal infusion rates. 5-alpha and 5-beta were tested on both young (44 to 46 days) and adult (109 to 118 days) rats. The relation between age and the anaesthetic sensitivity of 5-beta was tested by weekly threshold determinations. 5-alpha and 5-beta infused separately with different infusion rates gave almost V-shaped dose rate curves. The optimal infusion rate was in all age groups 2 mg/kg/min. In young rats 5-alpha (6.7 mg/kg) was more potent than 5-beta (8.9 mg/kg). In adult rats the sensitivity was increased but the relation in potency between 5-alpha (5.1 mg/kg) and 5-beta (6.6 mg/kg) was unchanged. With 5-beta the main change in this age-related increase in anaesthetic sensitivity was seen between 49 and 70 days of age. Both 5-alpha and 5-beta exhibited an excitatory action seen as jerks during induction of the EEG-criterion.