Non-anaesthetic steroids ameliorate the high pressure neurological syndrome in rats

The hypothesis that non-anaesthetic compounds, structurally related to specific anaesthetics, can protect against the high pressure neurological syndrome was tested. Infusion of two structural analogues of alphaxalone (3α-hydroxy-5α pregnane-11,20 dione) during pressurisation of rats with helium and oxygen gas mixtures (total pressure 80–100 ATA; inspired oxygen partial pressure 0.5 ATA) ameliorated the severe tremors associated with the high pressure neurological syndrome without any shift in tremor frequency (11–14 Hz). The steroid analogues which were selected (Δ16 and 3β-hydroxy-alphaxalone) have no known general anaesthetic effects and present an unexpected structural approach to the pharmacology of the syndrome. It may now be possible to investigate, treat or prevent the syndrome by the use of selective drugs without more generalised anaesthetic effects.