Neuroactive Steroids Hold Promise as Innovative Anesthetics

Drug Dev Res. 2025 Sep;86(6):e70137. doi: 10.1002/ddr.70137.

Abstract

Previous studies have shown that general anesthetics have neurotoxic effects on developing brains. Reducing the toxicity of anesthetics or finding nonneurotoxic anesthetics is a major challenge in anesthetic research. Neuroactive steroids (NASs) are active steroids in nervous tissue that regulate the excitability of the nervous system, γ-Aminobutyric acid subtype A receptors (GABAARs) serve as key targets in this regulatory process. NASs have many advantages in anesthesia, including rapid onset, mild cardiopulmonary inhibition, and neuroprotection, especially in recent studies showing that NASs do not cause neurotoxicity in the developing brain. NASs have the potential to return to human clinical applications, thereby assisting in clinical anesthesia. This article discusses the application prospects of NASs from the perspectives of action targets, drug characteristics, and neuroprotective effects, with a particular analysis of the possible mechanisms by which NASs do not induce neurotoxicity in anesthesia.

Keywords: GABAARs; NASs; neuroprotection.

Publication types

  • Review

MeSH terms

  • Anesthetics* / adverse effects
  • Anesthetics* / pharmacology
  • Animals
  • Brain / drug effects
  • Brain / growth & development
  • Brain / metabolism
  • Humans
  • Neuroprotective Agents* / pharmacology
  • Neurosteroids* / pharmacology
  • Receptors, GABA-A / metabolism
  • Steroids* / pharmacology

Substances

  • Anesthetics
  • Neurosteroids
  • Neuroprotective Agents
  • Receptors, GABA-A
  • Steroids