Abstract
Ion channel targeted drugs have always been related with either the central nervous system (CNS), the peripheral nervous system, or the cardiovascular system. Within the CNS, basic indications of drugs are: sleep disorders, anxiety, epilepsy, pain, etc. However, traditional channel blockers have multiple adverse events, mainly due to low specificity of mechanism of action. Lately, novel ion channel subtypes have been discovered, which gives premises to drug discovery process led towards specific channel subtypes. An example is Na+ channels, whose subtypes 1.3 and 1.7-1.9 are responsible for pain, and 1.1 and 1.2 – for epilepsy. Moreover, new drug candidates have been recognized. This review is focusing on ion channels subtypes, which play a significant role in current drug discovery and development process. The knowledge on channel subtypes has developed rapidly, giving new nomenclatures of ion channels. For example, Ca2+ channels are not any more divided to T, L, N, P/Q, and R, but they are described as Cav1.1-Cav3.3, with even newer nomenclature α1A-α1I and α1S. Moreover, new channels such as P2X1-P2X7, as well as TRPA1-TRPV1 have been discovered, giving premises for new types of analgesic drugs.
Highlights
Ion channels have been always related with drug discovery process
It was stated that blockade of TRPC1 and TRPP2 both by chemical inhibitors and by siRNA knockdown assays directed at TRPC1 and TRPP2 expression abolished the injury transient [Ca2+]i increase
This review shows that there is a significant progress in understanding etiopathogenesis and molecular biology in central nervous system (CNS) diseases, which have been a major challenge for decades
Summary
Ion channels have been always related with drug discovery process. Their types, primarily recognized as Na+, K+, Ca2+, Cl-, have been basically associated with neuronal processes. In contrary to other AEDs like carbamazepine, LCM probably affects sodium channel slow inactivation with no effect on fast inactivation This is a unique mechanism of action which results in preferentially block the electrical activity of neurons that are chronically depolarized but not those possessing more normal resting potentials [15, 58]. (13) exerts its antiepileptic activity by means of different mechanisms of action like VGSCs blockage, potentiation of GABAergic transmission, and AMPA receptor sites modulation It shows relatively broad spectrum of anticonvulsant properties in animal studies like MES (mice and rats), genetically seizure-prone DBA/2 mice, amygdala kindled rats. Ranalozine proved ability to cross the blood-brain barrier while tested in rats, which together with inhibition of persistent current in mutant NaV1.1 channels give rise for possible providing a new useful therapeutic strategy for SCN1A-associated epilepsy and some migraine syndroms [69]
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