ArticlePsychopharmacology2014
Anticonvulsant potencies of the enantiomers of the neurosteroids androsterone and etiocholanolone exceed those of the natural forms.
Article in Psychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Novel Synthetic Steroid Derivatives: Target Prediction and Biological Evaluation of Antiandrogenic Activity.Current issues in molecular biology · 2025Article
- New directions in neurosteroid therapeutics in neuropsychiatry.Neuroscience and biobehavioral reviews · 2025Review
- 5β-Dihydrosteroids: Formation and Properties.International journal of molecular sciences · 2024Review
- Exploring the mechanism of clomiphene citrate to improve ovulation disorder in PCOS rats based on follicular fluid metabolomics.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Neurosteroid enantiomers as potentially novel neurotherapeutics.Neuroscience and biobehavioral reviews · 2023Review
- An Integrative Transcriptome-Wide Analysis of Amyotrophic Lateral Sclerosis for the Identification of Potential Genetic Markers and Drug Candidates.International journal of molecular sciences · 2021Article
- Neurosteroids as novel antidepressants and anxiolytics: GABA-A receptors and beyond.Neurobiology of stress · 2019Article
- Anticonvulsant effects of isomeric nonimidazole histamine HDrug design, development and therapy · 2016Article
- Comparative Anticonvulsant Study of Epoxycarvone Stereoisomers.Molecules (Basel, Switzerland) · 2015Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
rationaleAndrosterone [(3α,5α)-3-hydroxyandrostan-17-one; 5α,3α-A] and its 5β-epimer etiocholanolone [(3α,5β)-3-hydroxyandrostan-17-one; 5β,3α-A)], the major excreted metabolites of testosterone, are neurosteroid positive modulators of GABAA receptors. Such neurosteroids typically show enantioselectivity in which the natural form is more potent than the corresponding unnatural enantiomer. For 5α,3α-A and 5β,3α-A, the unnatural enantiomers are more potent at GABAA receptors than the natural forms.
objectivesThe aim of this study was to compare the anticonvulsant potencies and time courses of 5α,3α-A and 5β,3α-A with their enantiomers in mouse seizure models.
methodsSteroids were administered intraperitoneally to male NIH Swiss mice 15 min (or up to 6 h in time course experiments) prior to administration of an electrical stimulus in the 6-Hz or maximal electroshock (MES) seizure tests or the convulsant pentylenetetrazol (PTZ).
resultsIn the 6-Hz test, the ED50 values of ent-5α,3α-A was 5.0 mg/kg whereas the value for 5α,3α-A was 12.1 mg/kg; the corresponding values in the PTZ seizure test were 22.8 and 51.8 mg/kg. Neurosteroid GABAA receptor-positive allosteric modulators are generally weak in the MES seizure test and this was confirmed in the present study. However, the atypical relative potency relationship was maintained with ED50 values of 140 and 223 mg/kg for ent-5α,3α-A and 5α,3α-A, respectively. Similar relationships were obtained for the 5β-isomers, except that the enantioselectivity was accentuated. In the 6-Hz and PTZ tests, the ED50 values of ent-5β,3α-A were 11.8 and 20.4 mg/kg whereas the values for 5β,3α-A were 57.6 and 109.1 mg/kg. Protective activity in the 6-Hz test of ent-5α,3α-A persisted for somewhat longer (~5 h) than for 5α,3α-A (~4 h); protection by ent-5β,3α-A also persisted longer (~3 h) than for 5β,3α-A (~2 h).
conclusionsThe unnatural enantiomers of 17-keto androgen class neurosteroids have greater in vivo potency and a longer duration of action than their natural counterparts. The more prolonged duration of action of the unnatural enantiomers could reflect reduced susceptibility to metabolism. Unnatural enantiomers of androgen class neurosteroids could have therapeutic utility and may provide advantages over the corresponding natural isomers due to enhanced potency and improved pharmacokinetic characteristics.
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