{"id":18644,"date":"2025-11-06T18:32:03","date_gmt":"2025-11-06T16:32:03","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=18644"},"modified":"2025-11-06T18:32:03","modified_gmt":"2025-11-06T16:32:03","slug":"2025-phentolamine-selectively-blocks-c-fiber-conduction-in-different-species-including-humans","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2025-phentolamine-selectively-blocks-c-fiber-conduction-in-different-species-including-humans\/","title":{"rendered":"2025 &#8211; Phentolamine selectively blocks C-fiber conduction in different species, including humans"},"content":{"rendered":"<div id=\"sec-1\" class=\"subsection\">\n<p id=\"p-1\"><strong>Background<\/strong>\u00a0Phentolamine is a non-selective competitive \u03b1-adrenergic antagonist clinically used to treat different vascular-related diseases. Since recent data suggest an antagonistic effect of phentolamine on voltage-gated sodium channels (VGSCs), further electrophysiological analysis is essential to understand its effects on peripheral sensory nerves.<\/p>\n<\/div>\n<div id=\"sec-2\" class=\"subsection\">\n<p id=\"p-2\"><strong>Methods<\/strong>\u00a0We examined the effects of phentolamine on the amplitude of the stimulus-evoked compound action potential (CAP) of A- and C-type nerve fibers derived from mice, pigs, and humans compared with the effects of lidocaine. To explore potential mechanisms of phentolamine action, we performed single nerve fiber recordings using skin-nerve preparations from wild-type and Na<sub>V<\/sub>1.8\/Na<sub>V<\/sub>1.9 double knockout mice, along with manual and automated whole-cell patch-clamp electrophysiology on ND7\/23 or HEK293 cells with heterologously expressed VGSCs.<\/p>\n<\/div>\n<div id=\"sec-3\" class=\"subsection\">\n<p id=\"p-3\"><strong>Results<\/strong>\u00a0Phentolamine decreased CAP amplitudes in a concentration-dependent manner, with significantly lower concentrations needed to affect C-fibers compared with A-fibers. Co-application of the \u03b1-adrenergic agonist (R)-(-)-phenylephrine did not alter this effect, suggesting that \u03b1-adrenergic receptors do not mediate phentolamine\u2019s action in this case. Phentolamine (100\u2009\u00b5M) inhibited the electrically evoked action potentials (AP) in the majority of single-unit cutaneous C-fibers, while the same concentration did not provoke AP extinction in A-fibers. C-fibers from Na<sub>V<\/sub>1.8\/Na<sub>V<\/sub>1.9 double knockout mice were significantly less sensitive to phentolamine than those from wild types. In patch-clamp experiments, phentolamine concentration-dependently blocked VGSCs, whereas Na<sub>V<\/sub>1.8 showed the highest sensitivity (IC<sub>50<\/sub>=10\u2009\u00b5M).<\/p>\n<\/div>\n<div id=\"sec-4\" class=\"subsection\">\n<p id=\"p-4\"><strong>Conclusions<\/strong>\u00a0Suppressing AP conduction and inhibiting VGSCs, phentolamine exhibits features reminiscent of local anesthetics, but with a stronger effect on C-fibers, which may be attributed to its stronger action on tetrodotoxin-resistant VGSCs. However, due to its markedly higher affinity for \u03b1-adrenergic receptors compared with VGSCs, systemic administration of phentolamine is limited by its adrenergic side effects. These findings suggest that phentolamine could be useful for exploring C-fiber function and provide a basis for the development of more selective and potent antinociceptive agents.<\/p>\n<\/div>\n","protected":false},"featured_media":0,"template":"","products_tags":[42],"resource_type":[75],"application_areas":[50,53,76],"therapeutic_areas":[143],"target_categories":[61],"target_families":[332],"targets":[],"resource_keyword":[],"class_list":["post-18644","resource_library","type-resource_library","status-publish","hentry","products_tags-syncropatch-384","resource_type-publication","application_areas-ion-channels","application_areas-assay-development-and-validation","application_areas-drug-discovery","therapeutic_areas-assay-development-and-validation","target_categories-voltage-gated-ion-channels","target_families-nav-channels"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/18644","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=18644"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=18644"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=18644"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=18644"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=18644"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=18644"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=18644"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=18644"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=18644"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}