scholarly journals Discovery of K V 1.3 ion channel inhibitors: Medicinal chemistry approaches and challenges

2021 ◽  
Author(s):  
Špela Gubič ◽  
Louise A. Hendrickx ◽  
Žan Toplak ◽  
Maša Sterle ◽  
Steve Peigneur ◽  
...  
Keyword(s):  
Ion Channel ◽  
Medicinal Chemistry ◽  
Ion Channel Inhibitors

scholarly journals Comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Lillian M. Toomey ◽  
Carole A. Bartlett ◽  
Nikolas Gavriel ◽  
Terence McGonigle ◽  
Maimuna Majimbi ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Ion Channel ◽  
Local Delivery ◽  
Nerve Transection ◽  
Secondary Degeneration ◽  
Injury Site ◽  
Myelin Structure ◽  
Ion Channel Inhibitors ◽  
Optic Nerve Transection ◽  
Inhibitor Combination

Abstract Injury to the central nervous system is exacerbated by secondary degeneration. Previous research has shown that a combination of orally and locally administered ion channel inhibitors following partial optic nerve injury protects the myelin sheath and preserves function in the ventral optic nerve, vulnerable to secondary degeneration. However, local administration is often not clinically appropriate. This study aimed to compare the efficacy of systemic and local delivery of the ion channel inhibitor combination of lomerizine, brilliant blue G (BBG) and YM872, which inhibits voltage-gated calcium channels, P2X7 receptors and Ca2+ permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors respectively. Following a partial optic nerve transection, adult female PVG rats were treated with BBG and YM872 delivered via osmotic mini pump directly to the injury site, or via intraperitoneal injection, both alongside oral administration of lomerizine. Myelin structure was preserved with both delivery modes of the ion channel inhibitor combination. However, there was no effect of treatment on inflammation, either peripherally or at the injury site, or on the density of oligodendroglial cells. Taken together, the data indicate that even at lower concentrations, the combinatorial treatment may be preserving myelin structure, and that systemic and local delivery are comparable at improving outcomes following neurotrauma.

scholarly journals Efficacy, Mechanism and Antiviral Resistance of Neuraminidase Inhibitors and Adamantane against Avian Influenza

2019 ◽  
Vol 29 (2) ◽  
pp. 61
Author(s):  
Dyah Ayu Hewajuli ◽  
NLPI Dharmayanti
Keyword(s):  
Avian Influenza ◽  
Ion Channel ◽  
Influenza A ◽  
Influenza Infection ◽  
Antiviral Drug ◽  
Neuraminidase Inhibitor ◽  
M2 Protein ◽  
New Variant ◽  
Amantadine Resistance ◽  
Ion Channel Inhibitors

Vaccination and antiviral drug are often used to control influenza. However, the effectiveness of vaccine was impaired due to the emergence of new variant of virus strain. Antiviral drug consists of prophylactic and curative substances, namely M2 ion channel inhibitors (adamantane; amantadine and rimantadine) and neuraminidase (NA) inhibitors (NAIs; oseltamivir, zanamivir, peramivir, laninamivir). The synthesis and modification of antiviral neuraminidase (NA) inhibitors (NAIs) and adamantanes increased the antiviral effectiveness. The mechanism of the neuraminidase inhibitor is to prevent influenza infection by inhibiting the release of the virus from internal cells. Adamantane is antiviral drug that selectively inhibits the flow of H+ ions through M2 protein to prevent the uncoating virus particles getting into the endosome. The substitution of (H275Y, S247N, I223L, K150N, R292K, I222T, R152K, R118K, E119V) on NA protein caused resistance of avian influenza virus against the neuraminidase inhibitor. The combination of mutations (S247N, I223L, K150N) increased the resistance of influenza A (H5N1) virus. The diffusion of adamantane resistance varies among HA subtypes, the species of host, the period of isolation, and region. Mutations at residues of 26, 27, 30, 31 or 34 transmembrane M2 protein caused adamantane resistance. The unique substitution (V27I) of M2 protein of clade 2.3.2 H5N1 subtype isolated in Indonesia in 2016 has been contributed to the amantadine resistance. Antiviral combination of M2 ion channel inhibitors and neuraminidase (NA) inhibitors is effective treatments for the resistance.

scholarly journals Delayed treatment of secondary degeneration following acute optic nerve transection using a combination of ion channel inhibitors

2017 ◽  
Vol 12 (2) ◽  
pp. 307 ◽  
Author(s):  
Melinda Fitzgerald ◽  
NathanaelJ Yates ◽  
MarcusK Giacci ◽  
RyanL O'Hare Doig ◽  
Wissam Chiha ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Ion Channel ◽  
Nerve Transection ◽  
Secondary Degeneration ◽  
Delayed Treatment ◽  
Ion Channel Inhibitors ◽  
Optic Nerve Transection

scholarly journals Development of Classification Model for hERG Ion Channel Inhibitors Using SVM Method

2009 ◽  
Vol 53 (6) ◽  
pp. 653-662 ◽  
Author(s):  
Sin-Moon Gang ◽  
Han-Jo Kim ◽  
Won-Seok Oh ◽  
Sun-Young Kim ◽  
Kyoung-Tai No ◽  
...  
Keyword(s):  
Ion Channel ◽  
Classification Model ◽  
Ion Channel Inhibitors

scholarly journals Identification of Isoform 2 Acid-Sensing Ion Channel Inhibitors as Tool Compounds for Target Validation Studies in CNS

2019 ◽  
Vol 10 (4) ◽  
pp. 627-632
Author(s):  
Leda Ivanova Bencheva ◽  
Marilenia De Matteo ◽  
Luca Ferrante ◽  
Marco Ferrara ◽  
Adolfo Prandi ◽  
...  
Keyword(s):  
Ion Channel ◽  
Validation Studies ◽  
Target Validation ◽  
Ion Channel Inhibitors

New Disaccharide-Based Ether Lipids as SK3 Ion Channel Inhibitors

ChemMedChem ◽  
2016 ◽  
Vol 11 (14) ◽  
pp. 1531-1539 ◽  
Author(s):  
Wilfried Berthe ◽  
Charlotte M. Sevrain ◽  
Aurélie Chantôme ◽  
Ana Maria Bouchet ◽  
Maxime Gueguinou ◽  
...  
Keyword(s):  
Ion Channel ◽  
Ether Lipids ◽  
Ion Channel Inhibitors

scholarly journals Virtual Screen for Repurposing of Drugs for Candidate Influenza a M2 Ion-Channel Inhibitors

2019 ◽  
Vol 9 ◽  
Author(s):  
Draginja Radosevic ◽  
Milan Sencanski ◽  
Vladimir Perovic ◽  
Nevena Veljkovic ◽  
Jelena Prljic ◽  
...  
Keyword(s):  
Ion Channel ◽  
Influenza A ◽  
Virtual Screen ◽  
Ion Channel Inhibitors
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