Results 21 to 30 of about 5,435 (219)

Cryo-EM reveals an unprecedented binding site for NaV1.7 inhibitors enabling rational design of potent hybrid inhibitors

eLife, 2023
The voltage-gated sodium (NaV) channel NaV1.7 has been identified as a potential novel analgesic target due to its involvement in human pain syndromes. However, clinically available NaV channel-blocking drugs are not selective among the nine NaV channel ...
Marc Kschonsak, Christine C Jao, Christopher P Arthur, Alexis L Rohou, Philippe Bergeron, Daniel F Ortwine, Steven J McKerrall, David H Hackos, Lunbin Deng, Jun Chen, Tianbo Li, Peter S Dragovich, Matthew Volgraf, Matthew R Wright, Jian Payandeh, Claudio Ciferri, John C Tellis   +16 more
doaj   +1 more source

Conserved but not critical: Trafficking and function of NaV1.7 are independent of highly conserved polybasic motifs

Frontiers in Molecular Neuroscience, 2023
Non-addictive treatment of chronic pain represents a major unmet clinical need. Peripheral voltage-gated sodium (NaV) channels are an attractive target for pain therapy because they initiate and propagate action potentials in primary afferents that ...
Sidharth Tyagi, Sidharth Tyagi, Sidharth Tyagi, Sidharth Tyagi, Nivedita Sarveswaran, Nivedita Sarveswaran, Nivedita Sarveswaran, Grant P. Higerd-Rusli, Grant P. Higerd-Rusli, Grant P. Higerd-Rusli, Grant P. Higerd-Rusli, Shujun Liu, Shujun Liu, Shujun Liu, Fadia B. Dib-Hajj, Fadia B. Dib-Hajj, Fadia B. Dib-Hajj, Stephen G. Waxman, Stephen G. Waxman, Stephen G. Waxman, Sulayman D. Dib-Hajj, Sulayman D. Dib-Hajj, Sulayman D. Dib-Hajj   +22 more
doaj   +1 more source

Distribution of Voltage-Gated Sodium Channels and Scaffolding Proteins on Vestibular Calyx Ending Delineates the Axon Initial Segment. [PDF]

J Comp Neurol
Various sodium channel isoforms and their scaffolding proteins are found in four different microdomains in vestibular calyx‐bearing afferents. These microdomains serve different purposes, analogous to the heminode, axon initial segment, and synaptic domains of other types of sensory afferents.
Lysakowski A, Govindaraju AC, Price SD, Gaboyard-Niay S, Calin-Jageman I, Chidavaenzi RL, Eatock RA, Raphael RM, Goldberg JM.   +8 more
europepmc   +2 more sources

Non-SUMOylated CRMP2 decreases NaV1.7 currents via the endocytic proteins Numb, Nedd4-2 and Eps15

Molecular Brain, 2021
Voltage-gated sodium channels are key players in neuronal excitability and pain signaling. Functional expression of the voltage-gated sodium channel NaV1.7 is under the control of SUMOylated collapsin response mediator protein 2 (CRMP2).
Kimberly Gomez, Dongzhi Ran, Cynthia L. Madura, Aubin Moutal, Rajesh Khanna   +4 more
doaj   +1 more source

Lacosamide Inhibition of Nav1.7 Voltage-Gated Sodium Channels: Slow Binding to Fast-Inactivated States [PDF]

Molecular Pharmacology, 2017
Lacosamide is an antiseizure agent that targets voltage-dependent sodium channels. Previous experiments have suggested that lacosamide is unusual in binding selectively to the slow-inactivated state of sodium channels, in contrast to drugs like carbamazepine and phenytoin, which bind tightly to fast-inactivated states.
Sooyeon, Jo, Bruce P, Bean
openaire   +2 more sources

Computational design of peptides to target NaV1.7 channel with high potency and selectivity for the treatment of pain

eLife, 2022
The voltage-gated sodium NaV1.7 channel plays a key role as a mediator of action potential propagation in C-fiber nociceptors and is an established molecular target for pain therapy.
Phuong T Nguyen, Hai M Nguyen, Karen M Wagner, Robert G Stewart, Vikrant Singh, Parashar Thapa, Yi-Je Chen, Mark W Lillya, Anh Tuan Ton, Richard Kondo, Andre Ghetti, Michael W Pennington, Bruce Hammock, Theanne N Griffith, Jon T Sack, Heike Wulff, Vladimir Yarov-Yarovoy   +16 more
doaj   +1 more source

Functional Studies of Interaction Between Huwentoxin-IV and Voltage-Gated Sodium Channel Nav1.7 [PDF]

Biophysical Journal, 2012
Voltage-gated sodium channel 1.7 (Nav1.7) plays a role in the conduction of action potentials and is involved in the sensation of pain. Spider toxins such as Huwentoxin IV (HwTx-IV) are potent inhibitors of Nav1.7, functioning as a gating modifier trapping the voltage sensor in an inward closed conformation.
Shih, Amy Y., Bembenek, Scott, Minassian, Natali, Neff, Robert, Liu, Yi, Flinspach, Mack, Edavettal, Suzanne, Wu, Nyantsz, Maher, Michael, Wickenden, Alan, Mirzadegan, Taraneh   +10 more
openaire   +1 more source

Targeting Voltage Gated Sodium Channels NaV1.7, NaV1.8, and NaV1.9 for Treatment of Pathological Cough [PDF]

Lung, 2013
Recent advances in our understanding of voltage-gated sodium channels (NaVs) lead to the rational hypothesis that drugs capable of selective blockade of NaV subtypes may be a safe and effective strategy for the treatment of unwanted cough. Among the nine NaV subtypes (NaV1.1-NaV1.9), the afferent nerves involved in initiating cough, in common with ...
Yukiko, Muroi, Bradley J, Undem
openaire   +2 more sources

Comparison of Gating Properties and Use-Dependent Block of Nav1.5 and Nav1.7 Channels by Anti-Arrhythmics Mexiletine and Lidocaine. [PDF]

PLoS ONE, 2015
Mexiletine and lidocaine are widely used class IB anti-arrhythmic drugs that are considered to act by blocking voltage-gated open sodium currents for treatment of ventricular arrhythmias and relief of pain.
Ying Wang, Jianxun Mi, Ka Lu, Yanxin Lu, KeWei Wang   +4 more
doaj   +1 more source

Suzetrigine, a Non-Opioid Small-Molecule Analgesic: Mechanism of Action, Clinical, and Translational Science. [PDF]

Clin Transl Sci
ABSTRACT The discovery and approval of Suzetrigine (VX‐548, Journavx) marks a significant breakthrough in pain management. It is the first non‐opioid analgesic approved since celecoxib in 1998. Suzetrigine selectively blocks voltage‐gated sodium channel Nav1.8 and acts exclusively on peripheral nociceptors without crossing the blood–brain barrier ...
Rajasingham R, Qi Y.
europepmc   +2 more sources