Alphaxalone, a neuroactive steroid containing a 17β-acetyl group, has potent anesthetic activity in humans. This pharmacological activity is attributed to this steroid's enhancement of γ-amino butyric acid-mediated chloride currents at γ-amino butyric acid type A receptors. The conversion of alphaxalone into Δ16-alphaxalone produces an analogue that lacks anesthetic activity in humans and that has greatly diminished receptor actions. By contrast, the corresponding 17β-carbonitrile analogue of alphaxalone and the Δ16-17-carbonitrile analogue both have potent anesthetic and receptor actions. The differential effect of the Δ16-double bond on the actions of alphaxalone and the 17β-carbonitrile analogue is accounted for by a differential effect on the orientation of the 17-acetyl and 17-carbonitrile substituents.

Original languageEnglish
Pages (from-to)6680-6684
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number22
StatePublished - Nov 15 2010


  • Alphaxalone
  • Anesthetic steroid
  • Delta-16-alphaxalone
  • GABA receptor
  • TBPS binding
  • Tadpole anesthesia


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