Neuroactive steroids alphaxalone and CDNC24 are effective hypnotics and potentiators of GABA
Animals
Apoptosis
/ drug effects
Brain
/ drug effects
Dose-Response Relationship, Drug
GABA-A Receptor Agonists
/ administration & dosage
Hippocampus
/ drug effects
Hypnotics and Sedatives
/ administration & dosage
Inhibitory Postsynaptic Potentials
/ drug effects
Neurotoxicity Syndromes
/ etiology
Prefrontal Cortex
/ drug effects
Pregnanediones
/ administration & dosage
Propofol
/ administration & dosage
Rats, Sprague-Dawley
Receptors, GABA-A
/ metabolism
Steroids
/ administration & dosage
Synapses
/ drug effects
general anaesthetic
prefrontal cortex
presynaptic
subiculum
synaptic transmission
synaptogenesis
Journal
British journal of anaesthesia
ISSN: 1471-6771
Titre abrégé: Br J Anaesth
Pays: England
ID NLM: 0372541
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
10
06
2019
revised:
01
01
2020
accepted:
20
01
2020
pubmed:
11
3
2020
medline:
10
5
2020
entrez:
11
3
2020
Statut:
ppublish
Résumé
The most currently used general anaesthetics are potent potentiators of γ-aminobutyric acid A (GABA The neurotoxic potential of CDNC24 was examined vis-à-vis propofol (2,6-diisopropylphenol) and alphaxalone (5α-pregnan-3α-ol-11,20-dione) at the peak of rat synaptogenesis. In addition to the morphological neurotoxicity studies of the subiculum and medial prefrontal cortex (mPFC), we assessed the extra-, pre-, and postsynaptic effects of these agents on GABAergic neurotransmission in acute subicular slices from rat pups. CDNC24, like alphaxalone and propofol, caused dose-dependent hypnosis in vivo, with a higher therapeutic index. CDNC24 and alphaxalone, unlike propofol, did not cause developmental neuroapoptosis in the subiculum and mPFC. Propofol potentiated post- and extrasynaptic GABA The lack of neurotoxicity of CDNC24 and alphaxalone may be at least partly related to suppression of presynaptic GABA release in the developing brain.
Sections du résumé
BACKGROUND
The most currently used general anaesthetics are potent potentiators of γ-aminobutyric acid A (GABA
METHODS
The neurotoxic potential of CDNC24 was examined vis-à-vis propofol (2,6-diisopropylphenol) and alphaxalone (5α-pregnan-3α-ol-11,20-dione) at the peak of rat synaptogenesis. In addition to the morphological neurotoxicity studies of the subiculum and medial prefrontal cortex (mPFC), we assessed the extra-, pre-, and postsynaptic effects of these agents on GABAergic neurotransmission in acute subicular slices from rat pups.
RESULTS
CDNC24, like alphaxalone and propofol, caused dose-dependent hypnosis in vivo, with a higher therapeutic index. CDNC24 and alphaxalone, unlike propofol, did not cause developmental neuroapoptosis in the subiculum and mPFC. Propofol potentiated post- and extrasynaptic GABA
CONCLUSIONS
The lack of neurotoxicity of CDNC24 and alphaxalone may be at least partly related to suppression of presynaptic GABA release in the developing brain.
Identifiants
pubmed: 32151384
pii: S0007-0912(20)30060-X
doi: 10.1016/j.bja.2020.01.013
pmc: PMC7222221
pii:
doi:
Substances chimiques
CDNC24 steroid
0
GABA-A Receptor Agonists
0
Hypnotics and Sedatives
0
Pregnanediones
0
Receptors, GABA-A
0
Steroids
0
alphaxalone
BD07M97B2A
Propofol
YI7VU623SF
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
603-613Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM123746
Pays : United States
Organisme : NICHD NIH HHS
ID : R21 HD080281
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD044517
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM118197
Pays : United States
Informations de copyright
Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
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