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[The diversity of mechanisms of the ion channels blockade as a way towards designing new pharmacological agents].

Dysfunctions of glutamatergic synaptic neurotransmission often accompany various CNS disorders. Action of excessive glutamate, which causes excitotoxic effects by neuron depolarization and massive calcium influx can lead to cell death. Despite obvious importance of development of anti-glutamic neuroprotectors, among great number of known antagonists of ionotropic glutamate receptors only memantine is used in medicinal practice. One of the sources of numerous side effects caused by glutamate receptor antagonists is that the drugs usually inhibit receptors, which mediate both normal and pathological CNS processes. A possible approach to overcoming the problem is to develop the drugs whose action is enhanced in potentially pathological conditions such as high-frequency activation, high glutamate concentration, depolarized membrane, etc. Action of many classes of antagonists depends on pattern of receptor activation and on membrane voltage. In the present work, we discuss several peculiarities of channel blocking mechanisms from the viewpoint of neuroprotector development. In particular, we compare channel blockers which demonstrate different types of interaction with the channel gating machinery, we consider different types of voltage dependence and consider action of channel blockers, which can permeate through the channel. We conclude that meticulous analysis of the mechanism of action of the glutamate receptor channel antagonists could help to approach predicting of in vivo action using in vitro data.