{"id":6534,"date":"2023-02-17T07:14:25","date_gmt":"2023-02-17T07:14:25","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2021-neuroactive-type-a-%ce%b3-aminobutyric-acid-receptor-allosteric-modulator-steroids-from-the-hypobranchial-gland-of-marine-mollusk-conus-geographus\/"},"modified":"2023-02-17T07:14:26","modified_gmt":"2023-02-17T07:14:26","slug":"2021-neuroactive-type-a-%ce%b3-aminobutyric-acid-receptor-allosteric-modulator-steroids-from-the-hypobranchial-gland-of-marine-mollusk-conus-geographus","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2021-neuroactive-type-a-%ce%b3-aminobutyric-acid-receptor-allosteric-modulator-steroids-from-the-hypobranchial-gland-of-marine-mollusk-conus-geographus\/","title":{"rendered":"2021 &#8211; Neuroactive Type-A \u03b3-Aminobutyric Acid Receptor Allosteric Modulator Steroids from the Hypobranchial Gland of Marine Mollusk, Conus geographus"},"content":{"rendered":"<p>In a program to identify pain treatments with low addiction potential, we isolated five steroids, conosteroids A\u2013E (1\u20135), from the hypobranchial gland of the mollusk Conus geographus. Compounds 1\u20135 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 \u03b3-aminobutyric acid receptors (GABAARs). In a patch-clamp experiment, out of the six subunit combinations tested, 6 exhibited subtype selectivity, most strongly antagonizing \u03b11\u03b21\u03b32 and \u03b14\u03b23\u03b32 receptors (IC<sub>50<\/sub> 1.5 and 1.0 \u03bcM, respectively). Although the structures of 1\u20136 differ from those of known neuroactive steroids, they are cell-type-selective modulators of GABAARs, expanding the known chemical space of neuroactive steroids.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[42],"resource_type":[75],"application_areas":[50,76],"therapeutic_areas":[56],"target_categories":[337],"target_families":[359],"targets":[],"resource_keyword":[],"class_list":["post-6534","resource_library","type-resource_library","status-publish","hentry","products_tags-syncropatch-384","resource_type-publication","application_areas-ion-channels","application_areas-drug-discovery","therapeutic_areas-pain","target_categories-ligand-gated-ion-channels","target_families-gabaa-receptors"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/6534","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/media?parent=6534"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=6534"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=6534"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=6534"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=6534"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=6534"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=6534"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=6534"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=6534"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}