Increased sodium channel use-dependent inhibition by a new potent analogue of tocainide greatly enhances in vivo antimyotonic activity
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چکیده
منابع مشابه
Increased sodium channel use-dependent inhibition by a new potent analogue of tocainide greatly enhances in vivo antimyotonic activity
Although the sodium channel blocker, mexiletine, is the first choice drug in myotonia, some myotonic patients remain unsatisfied due to contraindications, lack of tolerability, or incomplete response. More therapeutic options are thus needed for myotonic patients, which require clinical trials based on solid preclinical data. In previous structure-activity relationship studies, we identified tw...
متن کاملConstrained analogues of tocainide as potent skeletal muscle sodium channel blockers towards the development of antimyotonic agents.
1-Benzyl-N-(2,6-dimethylphenyl)piperidine-3-carboxamide and 4-benzyl-N-(2,6-dimethylphenyl)piperazine-2-carboxamide, two conformationally restricted analogues of tocainide, were designed and synthesized as voltage-gated skeletal muscle sodium channel blockers. They showed, with respect to tocainide, a marked increase in both potency and use-dependent block.
متن کاملCalixmexitil: Calixarene-based Cluster of Mexiletine with Amplified Anti-myotonic Activity as A Novel Use-dependent Sodium Channel Blocker
Mexiletine as the first choice drug in myotonia treatment is a chiral sodium channel blocker clinically used in its racemic form. The phenolic structure of this drug, prompted us to design its novel calix[4]arene-based cluster in a chalice-shaped structure. Therefore, the present study reports the synthesis and in-vitro anti-myotonic activity of the chalice-shaped cluster of mexiletine...
متن کاملCalixmexitil: Calixarene-based Cluster of Mexiletine with Amplified Anti-myotonic Activity as A Novel Use-dependent Sodium Channel Blocker
Mexiletine as the first choice drug in myotonia treatment is a chiral sodium channel blocker clinically used in its racemic form. The phenolic structure of this drug, prompted us to design its novel calix[4]arene-based cluster in a chalice-shaped structure. Therefore, the present study reports the synthesis and in-vitro anti-myotonic activity of the chalice-shaped cluster of mexiletine...
متن کاملThe mechanism of activity-dependent sodium channel inhibition by the antidepressants fluoxetine and desipramine.
The effect of monoamine uptake inhibitor-type antidepressants on sodium channels of hippocampal neurons was investigated. Members of the tricyclic group of antidepressants are known to modify multiple targets, including sodium channels, whereas selective serotonin-reuptake inhibitors (SSRIs) are regarded as highly selective compounds, and their effect on sodium channels was not investigated in ...
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ژورنال
عنوان ژورنال: Neuropharmacology
سال: 2017
ISSN: 0028-3908
DOI: 10.1016/j.neuropharm.2016.10.013