Pregnanolone emulsion

Høgskilde, S.; Jw, Nielsen; Carl, P; Mb, Sørensen

doi:10.1111/j.1365-2044.1987.tb03080.x

Cited by 29 publications

(2 citation statements)

References 16 publications

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“…This work includes a combination of understanding metabolism of endogenous neuroactive steroids, the relationship between steroid structure and anaesthesia, receptor subtypes responsible for hypnotic effects, and anaesthesia EEG correlates after treatment with synthetic neuroactive steroids. 7,[33][34][35][36][37][38][39][40][41] More recently, rodent models have been used to test the anaesthetic effects of several novel synthetic neuroactive steroids, such as ACN, 3β-OH, 3α-OH, and CDNC24 as hypnotic agents in adults and neonatal pups. 33,42,43 As can be seen in Figure 2, these synthetic compounds differ in their steroid structure at carbons 3 and 5, and CDNC24 has a further modification on the steroid D-ring.…”

Section: Rodent Modelsmentioning

confidence: 99%

“…Rodent models are the most common experimental animals used in studying the anaesthetic effects of neuroactive steroids and have helped elucidate the mechanisms by which neuroactive steroids exert these effects. This work includes a combination of understanding metabolism of endogenous neuroactive steroids, the relationship between steroid structure and anaesthesia, receptor subtypes responsible for hypnotic effects, and anaesthesia EEG correlates after treatment with synthetic neuroactive steroids 7,33‐41 . More recently, rodent models have been used to test the anaesthetic effects of several novel synthetic neuroactive steroids, such as ACN, 3β‐OH, 3α‐OH, and CDNC24 as hypnotic agents in adults and neonatal pups 33,42,43 .…”

Section: Animal Models Of Anaesthesiamentioning

confidence: 99%

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Synthetic neuroactive steroids as new sedatives and anaesthetics: Back to the future

Manzella

Covey

Jevtović-Todorović

et al. 2022

J Neuroendocrinology

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Since the 1990s, there has been waning interest in researching general anaesthetics (anaesthetics). Although currently used anaesthetics are mostly safe and effective, they are not without fault. In paediatric populations and neonatal animal models, they are associated with learning impairments and neurotoxicity. In an effort to research safer anaesthetics, we have gone back to re‐examine neuroactive steroids as anaesthetics. Neuroactive steroids are steroids that have direct, local effects in the central nervous system. Since the discovery of their anaesthetic effects, neuroactive steroids have been consistently used in human or veterinary clinics as preferred anaesthetic agents. Although briefly abandoned for clinical use due to unwanted vehicle side effects, there has since been renewed interest in their therapeutic value. Neuroactive steroids are safe sedative/hypnotic and anaesthetic agents across various animal species. Importantly, unlike traditional anaesthetics, they do not cause extensive neurotoxicity in the developing rodent brain. Similar to traditional anaesthetics, neuroactive steroids are modulators of synaptic and extrasynaptic γ‐aminobutyric acid type A (GABAA) receptors and their interactions at the GABAA receptor are stereo‐ and enantioselective. Recent work has also shown that these agents act on other ion channels, such as high‐ and low‐voltage‐activated calcium channels. Through these mechanisms of action, neuroactive steroids modulate neuronal excitability, which results in characteristic burst suppression of the electroencephalogram, and a surgical plane of anaesthesia. However, in addition to their interactions with voltage and ligand gated ions channels, neuroactive steroids interact with membrane bound metabotropic receptors and xenobiotic receptors to facilitate signaling of prosurvival, antiapoptotic pathways. These pathways play a role in their neuroprotective effects in neuronal injury and may also prevent extensive apoptosis in the developing brain during anaesthesia. The current review explores the history of neuroactive steroids as anaesthetics in humans and animal models, their diverse mechanisms of action, and their neuroprotective properties.

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Section: Rodent Modelsmentioning

confidence: 99%

Section: Animal Models Of Anaesthesiamentioning

confidence: 99%

Synthetic neuroactive steroids as new sedatives and anaesthetics: Back to the future

Manzella

Covey

Jevtović-Todorović

et al. 2022

J Neuroendocrinology

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Acute Toxicity of Substituted 2‐(1H‐pyrazol‐1‐yl)acetanilides and Related Commercially Available Local Anesthetics Toward Mice. A GRIND/ALMOND‐Based 3‐D QSAR Study

2009

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Alignment-free three-dimensional quantitative structure -toxicity relationship models, developed on the basis of GRid INdependent Descriptors (GRIND), on acute toxicity data obtained by (i) oral administration of 25 pyrazolylacetanilides, and (ii) intravenous administration of 15 commercially available Local Anesthetics (LAs) to mice was reported. The most favorable interaction regions extracted from molecular interaction fields obtained with HBA, HBD, hydrophobic, and shape probes were correlated with toxicity data expressed as log[1/(LD 50 )] by partial Least Square Analysis (PLS). Variable selection was done by fractional factorial design. The best PLS models for set (i) comprises 3LV with r 2 ¼ 0.95 and q 2 ¼ 0.72; for set (ii) comprises 2LV with r 2 ¼ 0.95 and q 2 ¼ 0.58. Internal cross-validation was done by using three random groups of compounds for each set. External predictivity of the second model was checked by a test set consists of eight structurally diverse compounds. The PLS model related to orally administrated set of compounds was compared with the corresponding one related to intravenously administrate drugs. Variables having high impact on each model, positively or negatively correlated with toxicities, were discussed and an attempt was made to link those variables with calculated ADME related properties of compounds, as well as with literature data that describes probable interaction of LA drugs with the homology modeled voltage-gated sodium channels. According to the best of our knowledge this is first reported study that use GRIND methodology in structure -toxicity relationships on whole animals.

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Sedative and hypnotic effects of oral administration of micronized progesterone may be mediated through its metabolites

Arafat

Hargrove

Maxson³

et al. 1988

American Journal of Obstetrics and Gynecology

129

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Pregnanolone emulsion

Abstract: SummaryThc r~niiesthetic uctivitj of' pregnanolonc (a nietoholitc gf' progcsteronc) Serious, and in some cases fatal, allergic reactions due to the Cremophor EL causcd this otherwise excellent drug to be withdrawn from clinical use.

Cited by 29 publications

References 16 publications

Synthetic neuroactive steroids as new sedatives and anaesthetics: Back to the future

Synthetic neuroactive steroids as new sedatives and anaesthetics: Back to the future

Acute Toxicity of Substituted 2‐(1H‐pyrazol‐1‐yl)acetanilides and Related Commercially Available Local Anesthetics Toward Mice. A GRIND/ALMOND‐Based 3‐D QSAR Study

Sedative and hypnotic effects of oral administration of micronized progesterone may be mediated through its metabolites

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