{"id":6277,"date":"2023-02-17T06:48:44","date_gmt":"2023-02-17T06:48:44","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2018-the-opioid-oxycodone-use%e2%80%90dependently-inhibits-the-cardiac-sodium-channel-nav1-5\/"},"modified":"2023-02-17T06:48:44","modified_gmt":"2023-02-17T06:48:44","slug":"2018-the-opioid-oxycodone-use%e2%80%90dependently-inhibits-the-cardiac-sodium-channel-nav1-5","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2018-the-opioid-oxycodone-use%e2%80%90dependently-inhibits-the-cardiac-sodium-channel-nav1-5\/","title":{"rendered":"2018 &#8211; The opioid oxycodone use\u2010dependently inhibits the cardiac sodium channel NaV1.5"},"content":{"rendered":"<p>BACKGROUND AND PURPOSE: Oxycodone is a potent semi-synthetic opioid that is commonly used for the treatment of severe acute and chronic pain. However, treatment with oxycodone can lead to cardiac electrical changes, such as long-QT syndrome, potentially inducing sudden cardiac arrest. Here, we investigate whether the cardiac side effects of oxycodone can be explained by modulation of the cardiac sodium channel NaV1.5. EXPERIMENTAL APPROACH: Heterologously expressed NaV1.5, NaV1.7 or NaV1.8 were used for whole-cell patch-clamp electrophysiology. A variety of voltage-clamp protocols was used to test the effect of oxycodone on different channel gating modalities. Human stem cell-derived cardiomyocytes were used to measure the effect of oxycodone on cardiomyocyte beating. KEY RESULTS: Oxycodone concentration-dependently and use-dependently inhibits NaV1.5 with an IC<sub>50<\/sub>\u00a0of 483.2 \u03bcM. In addition, oxycodone slows recovery of NaV1.5 from fast inactivation and increases slow inactivation. At high concentrations, these effects lead to a reduced beat rate in cardiomyocytes and to arrhythmia. In contrast, no effects could be observed on NaV1.7 or NaV1.8. CONCLUSION AND IMPLICATIONS: Oxycodone leads to an accumulation of NaV1.5 in inactivated states with a slow time course. While the concentrations needed to elicit cardiac arrhythmia in vitro are comparably high, some patients under long-term treatment with oxycodone as well as drug abusers and addicts might suffer from severe cardiac side effects induced by the slow effects of oxycodone on NaV1.5.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[34],"resource_type":[75],"application_areas":[50,76,77],"therapeutic_areas":[54,56],"target_categories":[61],"target_families":[332],"targets":[93,116,117],"resource_keyword":[],"class_list":["post-6277","resource_library","type-resource_library","status-publish","hentry","products_tags-cardioexcyte-96","resource_type-publication","application_areas-ion-channels","application_areas-drug-discovery","application_areas-cell-ipscs-profiling","therapeutic_areas-cardiac-safety-cipa","therapeutic_areas-pain","target_categories-voltage-gated-ion-channels","target_families-nav-channels","targets-nav1-5","targets-nav1-7","targets-nav1-8"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/6277","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=6277"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=6277"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=6277"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=6277"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=6277"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=6277"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=6277"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=6277"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=6277"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}