Supratherapeutic Phenytoin Therapy in Drug-Refractory Genetic Sodium Channel Epilepsies

Kesavan, Shivan; Kumar, Sandeep; Periyakaruppan, Muthiah; Kandasamy, Sasidaran; Murugesan, Gnanabalan

doi:10.1007/s12098-022-04224-x

Cited by 2 publications

(1 citation statement)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…23 It is well documented that genetic factors play a significant role in the modulation of anti-seizures medications efficacy, adverse effects, and dose changes such as phenytoin, carbamazepine, sodium valproate. 24,25 Enhanced gap junctional communication (GJC) between neurons is considered a major factor underlying the neuronal synchrony driving seizure activity. In drug-resistant epilepsy, connexins, as integral components of gap junctions, are implicated in several key processes contributing to the resistance to antiepileptic drugs (AEDs).…”

Section: Role Of Connexins In Epilepsymentioning

confidence: 99%

Pharmacology of Connexins-Still a Gap

Venkatraman,

Ramasamy

2024

J. Young Pharm.

View full text Add to dashboard Cite

Between the cells are present the gap junctions which are made up of proteins named connexins. The connexin family in humans has cell-specific roles consisting of 21 members and the most studied one is connexin 43. Connexins have a ubiquitous distribution and their function is in cell-cell communication and also a site for protein-protein interactions in regulating the signaling pathways. Their half-life is very short for 5 hours with Cx46 present in lens fibres and Cx30 in keratinocytes being the exceptions. The normal physiology ensures the complete role of connexins and their dysfunction may result in genetic disorders (Eg: Mutations in Cx32 result in Charcot-Marie-Tooth neuropathy X type 1 characterised by progressive peripheral neuropathy), delayed wound healing, arrhythmia, etc. Its role in cancer is very complex making the connexins act as both suppressor and promoter for tumor progression. In therapeutics, connexins peptide mimetics are a good option since they mimic a particular sequence of connexins which enhances their specificity and inhibits the function of gap junction in animal models. By binding to the mRNA of connexins, antisense oligodeoxynucleotides downregulate connexins useful in skin wound healing and also in eye infections where treatment with AsODN was found to reduce scarring in animal studies. Repurposed drugs like modafinil and flecainide as low-dose glial connexin modulators and identification of the activity of clofazimine against connexins in trials show that targeting connexins shows promise in the future. Connexin modulators are now in trials for wound healing and to avoid off-targets, it is applied topically as a gel. This review will deal with the physiological role and highlight the pathological condition for which connexins can be a therapeutic target.

show abstract

Section: Role Of Connexins In Epilepsymentioning

confidence: 99%