ArticleBritish journal of anaesthesia2018
A neurosteroid analogue with T-type calcium channel blocking properties is an effective hypnotic, but is not harmful to neonatal rat brain.
Article in British journal of anaesthesia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Sevoflurane, but not alphaxalone, causes lasting autism spectrum disorder-like pathology in male mice after exposure occurs during synaptogenesis.Neuropharmacology · 2026Article
- Electrophysiological Characterization of Sex-Dependent Hypnosis by an Endogenous Neuroactive Steroid Epipregnanolone.Biomolecules · 2025Article
- From neurotoxicity to neuroprotection: Rethinking GABACell biology and toxicology · 2025Review
- New directions in neurosteroid therapeutics in neuropsychiatry.Neuroscience and biobehavioral reviews · 2025Review
- Review
- Neurosteroids: mechanistic considerations and clinical prospects.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- The Role of Neuroactive Steroids in Analgesia and Anesthesia: An Interesting Comeback?Biomolecules · 2023Review
- Neonatal exposure to a neuroactive steroid alters low-frequency oscillations in the subiculum.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Sex-specific hypnotic effects of the neuroactive steroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile are mediated by peripheral metabolism into an active hypnotic steroid.British journal of anaesthesia · 2023Article
- CaInternational journal of molecular sciences · 2022Review
- Thalamic T-Type Calcium Channels as Targets for Hypnotics and General Anesthetics.International journal of molecular sciences · 2022Review
- General Anesthesia and the Young Brain: The Importance of Novel Strategies with Alternate Mechanisms of Action.International journal of molecular sciences · 2022Review
- Synthetic neuroactive steroids as new sedatives and anaesthetics: Back to the future.Journal of neuroendocrinology · 2022Review
- Physiological markers of rapid antidepressant effects of allopregnanolone.Journal of neuroendocrinology · 2022Review
- Do We Have Viable Protective Strategies against Anesthesia-Induced Developmental Neurotoxicity?International journal of molecular sciences · 2022Review
- Further Evidence that Inhibition of Neuronal Voltage-Gated Calcium Channels Contributes to the Hypnotic Effect of Neurosteroid Analogue, 3β-OH.Frontiers in pharmacology · 2022Article
- Different roles of T-type calcium channel isoforms in hypnosis induced by an endogenous neurosteroid epipregnanolone.Neuropharmacology · 2021Article
- Differential effects of the novel neurosteroid hypnotic (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile on electroencephalogram activity in male and female rats.British journal of anaesthesia · 2021Article
- The T-type calcium channel isoform CaBritish journal of anaesthesia · 2021Article
- Neonatal Isoflurane Does Not Affect Sleep Architecture and Minimally Alters Neuronal Beta Oscillations in Adolescent Rats.Frontiers in behavioral neuroscience · 2021Article
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10 authors.
Funding
Abstract
backgroundMore than 4 million children are exposed annually to sedatives and general anaesthetics (GAs) in the USA alone. Recent data suggest that common GAs can be detrimental to brain development causing neurodegeneration and long-term cognitive impairments. Challenged by a recent US Food and Drug Administration (FDA) warning about potentially neurotoxic effects of GAs in children, there is an urgent need to develop safer GAs.
methodsPostnatal Day 7 (P7) rat pups of both sexes were exposed to six (repeated every 2 h) injections of equipotent hypnotic doses of ketamine or the neuroactive steroid (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH) for 12 h. Loss of righting reflex was used to assess hypnotic properties and therapeutic index; quantitative caspase-3 immunohistochemistry was used to assess developmental neuroapoptosis; patch-clamp recordings in acute brain slices were used to assess the effects of 3β-OH on neuronal excitability and synaptic transmission. Cognitive abilities of rats exposed to ketamine, 3β-OH, or vehicle at P7 were assessed in young adulthood using the radial arm maze.
resultsThe neuroactive steroid 3β-OH has a therapeutic index similar to ketamine, a commonly used clinical GA. We report that 3β-OH is safe and, unlike ketamine, does not cause neuroapoptosis or impair cognitive development when administered to P7 rat pups. Interestingly, 3β-OH blocks T-type calcium channels and presynaptically dampens synaptic transmission at hypnotically-relevant brain concentrations, but it lacks a direct effect on γ-aminobutyric acid A or glutamate-gated ion channels.
conclusionsThe neurosteroid 3β-OH is a relatively safe hypnotic that warrants further consideration for paediatric anaesthesia.
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