The Anaesthetic Potency of 3α‐Hydroxy‐5α‐pregnan‐20‐one and 3α‐Hydroxy‐5β‐pregnan‐20‐one Determined with an Intravenous EEG‐Threshold Method in Male Rats

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Abstract
Two progesterone metabolites 3α-hydroxy-5α-pregnan-20-one (5-α) and 3α-hydroxy-5β-pregnan-20-one (5-β) were investigated for anaesthetic potency in male rats with an EEG-threshold method. Dose rate curves were obtained by infusing 5-α and 5β 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-α and 5-β 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-β was tested by weekly threshold determinations. 5-α and 5-β 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-α (6.7 mg/kg) was more potent than 5-β (8.9 mg/kg). In adult rats the sensitivity was increased but the relation in potency between 5-α (5.1 mg/kg) and 5-β (6.6 mg/kg) was unchanged. With 5-β the main change in this age-related increase in anaesthetic sensitivity was seen between 49 and 70 days of age. Both 5-α and 5-β exhibited an excitatory action seen as jerks during induction of the EEG-criterion.