22118-12-3Relevant articles and documents
Inhibition of inflammatory pain and cough by a novel charged sodium channel blocker
Tochitsky, Ivan,Jo, Sooyeon,Andrews, Nick,Kotoda, Masakazu,Doyle, Benjamin,Shim, Jaehoon,Talbot, Sebastien,Roberson, David,Lee, Jinbo,Haste, Louise,Jordan, Stephen M.,Levy, Bruce D.,Bean, Bruce P.,Woolf, Clifford J.
, p. 3905 - 3923 (2021)
Background and Purpose: Many pain-triggering nociceptor neurons express TRPV1 or TRPA1, cation-selective channels with large pores that enable permeation of QX-314, a cationic analogue of lidocaine. Co-application of QX-314 with TRPV1 or TRPA1 activators can silence nociceptors. In this study, we describe BW-031, a novel more potent cationic sodium channel inhibitor, and test whether its application alone can inhibit pain associated with tissue inflammation and whether this strategy can also inhibit cough. Experimental Approach: We tested the ability of BW-031 to inhibit pain in three models of tissue inflammation:- inflammation in rat paws produced by complete Freund's adjuvant or by surgical incision and a mouse ultraviolet (UV) burn model. We tested the ability of BW-031 to inhibit cough induced by inhalation of dilute citric acid in guinea pigs. Key Results: BW-031 inhibited Nav1.7 and Nav1.1 channels with approximately sixfold greater potency than QX-314 when introduced inside cells. BW-031 inhibited inflammatory pain in all three models tested, producing more effective and longer-lasting inhibition of pain than QX-314 in the mouse UV burn model. BW-031 was effective in reducing cough counts by 78%–90% when applied intratracheally under isoflurane anaesthesia or by aerosol inhalation in guinea pigs with airway inflammation produced by ovalbumin sensitization. Conclusion and Implications: BW-031 is a novel cationic sodium channel inhibitor that can be applied locally as a single agent to inhibit inflammatory pain. BW-031 can also effectively inhibit cough in a guinea pig model of citric acid-induced cough, suggesting a new clinical approach to treating cough.
PHOSPHONIUM ION CHANNEL BLOCKERS AND METHODS FOR USE
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Paragraph 0177; 0182-0183, (2021/05/07)
The invention provides compounds of Formula (I), or pharmaceutically acceptable salts thereof: The compounds, compositions, methods and kits of the invention are useful for the treatment of pain, itch, and neurogenic inflammation.
Method and using tracer charged ion channel
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Paragraph 0311; 0313; 0314-0316, (2018/08/20)
The invention provides compounds, compositions, methods, and kits for the treatment of pain, itch, and neurogenic inflammation.
