{"id":6256,"date":"2023-02-17T07:03:07","date_gmt":"2023-02-17T07:03:07","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2018-non-blocking-modulation-contributes-to-sodium-channel-inhibition-by-a-covalently-attached-photoreactive-riluzole-analog\/"},"modified":"2023-02-17T07:03:08","modified_gmt":"2023-02-17T07:03:08","slug":"2018-non-blocking-modulation-contributes-to-sodium-channel-inhibition-by-a-covalently-attached-photoreactive-riluzole-analog","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2018-non-blocking-modulation-contributes-to-sodium-channel-inhibition-by-a-covalently-attached-photoreactive-riluzole-analog\/","title":{"rendered":"2018 &#8211; Non-blocking modulation contributes to sodium channel inhibition by a covalently attached photoreactive riluzole analog"},"content":{"rendered":"<p>Sodium channel inhibitor drugs decrease pathological hyperactivity in various diseases including pain syndromes, myotonia, arrhythmias, nerve injuries and epilepsies. Inhibiting pathological but not physiological activity, however, is a major challenge in drug development. Sodium channel inhibitors exert their efects by a dual action: they obstruct ion fow (\u201cblock\u201d), and they alter the energetics of channel opening and closing (\u201cmodulation\u201d). Ideal drugs would be modulators without blocking effect, because modulation is inherently activity-dependent, therefore selective for pathological hyperactivity. Can block and modulation be separated? It has been difficult to tell, because the effect of modulation is obscured by conformation-dependent association\/dissociation of the drug. To eliminate dynamic association\/dissociation, we used a photoreactive riluzole analog which could be covalently bound to the channel; and found, unexpectedly, that drug-bound channels could still conduct ions, although with modulated gating. The finding that non-blocking modulation is possible, may open a novel avenue for drug development because non-blocking modulators could be more specifc in treating hyperactivity-linked diseases.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[45],"resource_type":[75],"application_areas":[50,76],"therapeutic_areas":[55,56],"target_categories":[61],"target_families":[332],"targets":[263],"resource_keyword":[],"class_list":["post-6256","resource_library","type-resource_library","status-publish","hentry","products_tags-port-a-patch","resource_type-publication","application_areas-ion-channels","application_areas-drug-discovery","therapeutic_areas-cns","therapeutic_areas-pain","target_categories-voltage-gated-ion-channels","target_families-nav-channels","targets-nav1-4"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/6256","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=6256"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=6256"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=6256"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=6256"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=6256"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=6256"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=6256"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=6256"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=6256"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}