دورية أكاديمية
Neuroactive Type-A γ-Aminobutyric Acid Receptor Allosteric Modulator Steroids from the Hypobranchial Gland of Marine Mollusk, Conus geographus .
| العنوان: | Neuroactive Type-A γ-Aminobutyric Acid Receptor Allosteric Modulator Steroids from the Hypobranchial Gland of Marine Mollusk, Conus geographus . |
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| المؤلفون: | Niu C; Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, United States., Leavitt LS; School of Biological Sciences, University of Utah, Salt Lake City, Utah 84112, United States., Lin Z; Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, United States., Paguigan ND; Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, United States., Sun L; Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, United States., Zhang J; Department of Anesthesiology, School of Medicine, University of Utah, Salt Lake City, Utah 84112, United States., Torres JP; Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, United States., Raghuraman S; School of Biological Sciences, University of Utah, Salt Lake City, Utah 84112, United States., Chase K; School of Biological Sciences, University of Utah, Salt Lake City, Utah 84112, United States., Cadeddu R; Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, United States., Karthikeyan M; School of Biological Sciences, University of Utah, Salt Lake City, Utah 84112, United States., Bortolato M; Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, United States., Reilly CA; Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah 84112, United States., Hughen RW; Department of Anesthesiology, School of Medicine, University of Utah, Salt Lake City, Utah 84112, United States., Light AR; Department of Anesthesiology, School of Medicine, University of Utah, Salt Lake City, Utah 84112, United States., Olivera BM; School of Biological Sciences, University of Utah, Salt Lake City, Utah 84112, United States., Schmidt EW; Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, United States. |
| المصدر: | Journal of medicinal chemistry [J Med Chem] 2021 May 27; Vol. 64 (10), pp. 7033-7043. Date of Electronic Publication: 2021 May 05. |
| نوع المنشور: | Journal Article; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 9716531 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4804 (Electronic) Linking ISSN: 00222623 NLM ISO Abbreviation: J Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington Dc : American Chemical Society Original Publication: [Easton, Pa.] : American Chemical Society, [c1963- |
| مواضيع طبية MeSH: | Analgesics/*chemistry , Conus Snail/*chemistry , GABA Antagonists/*chemistry , Neurosteroids/*chemistry , Receptors, GABA/*chemistry, Action Potentials/drug effects ; Analgesics/chemical synthesis ; Analgesics/pharmacology ; Analgesics/therapeutic use ; Animals ; Conus Snail/metabolism ; Disease Models, Animal ; GABA Antagonists/isolation & purification ; GABA Antagonists/pharmacology ; GABA Antagonists/therapeutic use ; Ganglia, Spinal/cytology ; Ganglia, Spinal/drug effects ; Ganglia, Spinal/physiology ; Mice ; Mice, Inbred C57BL ; Molecular Conformation ; Neurosteroids/isolation & purification ; Neurosteroids/pharmacology ; Neurosteroids/therapeutic use ; Pain/chemically induced ; Pain/drug therapy ; Pain/pathology ; Protein Subunits/chemistry ; Protein Subunits/metabolism ; Receptors, GABA/metabolism |
| مستخلص: | In a program to identify pain treatments with low addiction potential, we isolated five steroids, conosteroids A-E ( 1 - 5 ), from the hypobranchial gland of the mollusk Conus geographus . Compounds 1 - 5 were active in a mouse dorsal root ganglion (DRG) assay that suggested that they might be analgesic. A synthetic analogue 6 was used for a detailed pharmacological study. Compound 6 significantly increased the pain threshold in mice in the hot-plate test at 2 and 50 mg/kg. Compound 6 at 500 nM antagonizes type-A γ-aminobutyric acid receptors (GABA |
| المشرفين على المادة: | 0 (Analgesics) 0 (GABA Antagonists) 0 (Neurosteroids) 0 (Protein Subunits) 0 (Receptors, GABA) |
| تواريخ الأحداث: | Date Created: 20210505 Date Completed: 20210621 Latest Revision: 20210621 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1021/acs.jmedchem.1c00562 |
| PMID: | 33949869 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1520-4804 |
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| DOI: | 10.1021/acs.jmedchem.1c00562 |