Functional characterization of sodium channel blockers by membrane potential measurements in cerebellar neurons: Prediction of compound preference for the open/inactivated state

Kolok, Sándor; Nagy, J; Szombathelyi, Zsolt; Tarnawa, Istvàn

doi:10.1016/j.neuint.2006.04.014

Cited by 11 publications

(4 citation statements)

References 54 publications

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“…The VGNC blocker tetrodotoxin (TTX) was used as standard in these experiments. 78 In parallel, we tested the neuroprotective activity of compounds 15-38 against a model of τ hyperphosphorylation, by stimulating SH-SY5Y neuroblastoma cells with the PPP selective inhibitor OA. SH-SY5Y cells suffered a fall of 35% in their viability when exposed for 20 h to OA 20 nM.…”

Section: Resultsmentioning

confidence: 99%

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Gramine Derivatives Targeting Ca²⁺ Channels and Ser/Thr Phosphatases: A New Dual Strategy for the Treatment of Neurodegenerative Diseases

et al. 2016

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Section: Resultsmentioning

confidence: 99%

“…Again, benzyl and butyl groups branched to the indole nitrogen afforded the best neuroprotection (Table ). The VGNC blocker tetrodotoxin (TTX) was used as standard in these experiments …”

Section: Resultsmentioning

confidence: 99%

Gramine Derivatives Targeting Ca²⁺ Channels and Ser/Thr Phosphatases: A New Dual Strategy for the Treatment of Neurodegenerative Diseases

et al. 2016

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“…Again, the drawback of these fluorescent methods is that they usually do not supply information about the state-dependence of drug action and (usually) use veratridine to open channels. A recent paper [137] reports that the potency of statedependent blockers is considerably higher if they are applied when the cells are already depolarized by veratridine compared with the situation when the activator is added following pre-incubation with the drug. No similar difference between the potencies of state-independently acting compounds (such as GBR 12909; 1-[2-[bis(4-fluorophenyl) methoxy]ethyl]-4-(3-phenylpropyl)piperazine) was found.…”

Section: Methods For Testing Vgsc Blockersmentioning

confidence: 99%

Blockers of Voltage-Gated Sodium Channels for the Treatment of Central Nervous System Diseases

Tarnawa¹,

Bölcskei²,

Kocsis

2007

RPCN

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Voltage gated sodium channels play important roles both in vital physiological functions and several pathological processes of the central nervous system. Epilepsy, chronic pain, neurodegenerative diseases, and spasticity are all characterized by an over-excited state of specific groups of central neurons that is accompanied by an abnormally increased activity of sodium channels. An efficient strategy of controlling such diseases is to use blockers that preferentially act on these over-excited cells. State dependently acting agents, such as phenytoin, or lamotrigine, leave normal physiological functions relatively intact, resulting in a favorable therapeutic window. Nine isoforms of the channel forming alpha subunit are known, which show distinct expression patterns in different tissues. Another possible way to decrease the chance of adverse effects is to develop agents selectively inhibiting the channel subtype involved in the pathomechanism of the disease to be treated. Many recent patents claim sodium channel blockers with improved characteristics regarding state dependency or subtype selectivity. Such agents may offer a breakthrough in the treatment of a variety of central nervous system diseases. This review focuses on the current trends in sodium channel research, surveying the traditional and newly emerging therapeutic fields, and the diverse medicinal chemistry of sodium channel blockers.

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“…The limitations of 3H-BTX binding in lead identification and optimization have now been generally recognized (Chazot 2001;Tarnawa et al, 2007). Novel test systems such as automated patch clamping (Kiss et al, 2003), or plate-reader-based fluorescent membrane potential measurements (Kolok et al, 2006) are just beginning to appear. Thus, old VGSC blockers -the mechanism of which was generally recognized a long time after their introduction as therapies -are frequently used as leads for drug design.…”

Section: Efforts To Identify New Vgsc Blocking Structuresmentioning

confidence: 99%

Voltage-gated sodium channel blockers, 2001-2006: An overview

2007

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Voltage-gated sodium channel blockers have long been used in the therapy of various central nervous system diseases, including epilepsy, chronic pain, psychiatric disorders, and spasticity. Several old agents are available with suboptimal features. Their properties may be improved by enhancing their statedependent channel blocking action, and/or sodium channel subtype selectivity. This paper gives a short overview on the present state of research in this field, and the chemical structures of old sodium channel blockers, and those of recently published or patented compounds with sodium channel blocking action.

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Functional characterization of sodium channel blockers by membrane potential measurements in cerebellar neurons: Prediction of compound preference for the open/inactivated state

Cited by 11 publications

References 54 publications

Gramine Derivatives Targeting Ca²⁺ Channels and Ser/Thr Phosphatases: A New Dual Strategy for the Treatment of Neurodegenerative Diseases

Gramine Derivatives Targeting Ca²⁺ Channels and Ser/Thr Phosphatases: A New Dual Strategy for the Treatment of Neurodegenerative Diseases

Blockers of Voltage-Gated Sodium Channels for the Treatment of Central Nervous System Diseases

Voltage-gated sodium channel blockers, 2001-2006: An overview

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Functional characterization of sodium channel blockers by membrane potential measurements in cerebellar neurons: Prediction of compound preference for the open/inactivated state

Cited by 11 publications

References 54 publications

Gramine Derivatives Targeting Ca2+ Channels and Ser/Thr Phosphatases: A New Dual Strategy for the Treatment of Neurodegenerative Diseases

Gramine Derivatives Targeting Ca2+ Channels and Ser/Thr Phosphatases: A New Dual Strategy for the Treatment of Neurodegenerative Diseases

Blockers of Voltage-Gated Sodium Channels for the Treatment of Central Nervous System Diseases

Voltage-gated sodium channel blockers, 2001-2006: An overview

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Product

Resources

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Gramine Derivatives Targeting Ca²⁺ Channels and Ser/Thr Phosphatases: A New Dual Strategy for the Treatment of Neurodegenerative Diseases

Gramine Derivatives Targeting Ca²⁺ Channels and Ser/Thr Phosphatases: A New Dual Strategy for the Treatment of Neurodegenerative Diseases