Potent sodium channel blockers. Medical search. Frequent questions

Class II drugs are beta-blockers, which affect predominantly slow-channel tissues (sinoatrial [SA] and atrioventricular [AV] nodes), where they decrease rate of automaticity, slow conduction velocity, and prolong refractoriness. (msdmanuals.com)
Thus, there is concern primarily about use of epinephrine, lidocaine, and beta-blockers in the setting of acute cocaine toxicity. (medscape.com)
For instance, beta-blockers, a type of blood pressure medicine, can disturb the body's ability to channel potassium to where it is needed. (md-health.com)

Plugging one particular type of channel, known as NaV1.7, keeps the cell from passing a pain message to other parts of the body, as discussed in the accompanying article. (scientificamerican.com)
Since the main subtype of sodium channels involved in pain signaling is Nav1.7, its important that potential inhibitors target this subtype with high efficacy and in a selective manner. (elifesciences.org)
In this manuscript, the authors set out to improve on a peptide, ProTxII, which had been previously put forward as a promising blocker of Nav1.7 channels. (elifesciences.org)
make use of recently determined cryo-EM structures of Nav1.7 channels in complex with ProTX-II, a peptide spider toxin that binds to VSD2 and stabilizes the deactivated state of the channel in addition to reducing peak currents. (elifesciences.org)
Previous work on making modified spider toxin peptides as potent and selective Nav1.7 inhibitors by Merck, Amgen, and others was conducted in a structure-blind manner. (elifesciences.org)
Overall, this is an excellent investigation into the feasibility of using structural information and computational tools to design potent and selective Nav1.7 inhibitors. (elifesciences.org)
ICA-121431 is a potent, selective inhibitor of the human Nav1.3 and Nav1.1 voltage gated sodium channels (IC50 = 19 nM) with little or no activity against human Nav1.5 or Nav1.7 channels. (xcessbio.com)

Studies of these toxins have focused on varied aspects of venom peptides ranging from evolutionary relationships of predator and prey, biological actions on excitable tissues, potential application as pharmacological intervention in disease therapy, and as part of multiple experimental approaches towards an understanding of the atomistic characterization of ion channel structure. (mdpi.com)
This review examines the historical perspective of the study of conotoxin peptides active on sodium channels gated by transmembrane voltage, which has led to recent advances in ion channel research made possible with the exploitation of the diversity of these marine toxins. (mdpi.com)

Dalfampridine, a broad-spectrum potassium blocker is approved as a treatment to improve walking in patients with MS. The improvement in walking was demonstrated by an increase in walking speed. (medscape.com)
Potassium-channel openers are drugs that activate (open) ATP-sensitive K + -channels in vascular smooth muscle. (cvpharmacology.com)
Being effective arterial dilators, potassium-channel openers are used in the treatment of hypertension . (cvpharmacology.com)
Although several potassium-channel openers have been used in research for many years, only one, minoxidil , is approved for humans to treat hypertension. (cvpharmacology.com)
Class III drugs are primarily potassium channel blockers, which prolong action potential duration and refractoriness in slow- and fast-channel tissues. (msdmanuals.com)
Sodium loss causes secondary loss of potassium, which is particu-larly hazardous if the patient is to be given digitalis. (brainkart.com)
That's an indication of muscle overuse and inadequate electrolytes (potassium, sodium and magnesium), and too much calcium (which triggers muscle contractions). (maxcelint.com)
Although Amiloride Hydrochloride may be used alone, its principal indication is as concurrent therapy with thiazides or more potent diuretics in order to conserve potassium during periods of vigorous diuresis and during long-term maintenance therapy. (janusinfo.se)

Furthermore, the DSC1 channel is insensitive to tetrodotoxin, a potent and specific sodium channel blocker. (duke.edu)
INTRODUCTION: Tetrodotoxin (TTX) is a potent sodium channel blocker, with significant neurotoxicity, found in marine animals like pufferfish and blue-ringed octopus. (cdc.gov)
In the voltage-clamp mode, holding at -60 mV, the borneol-induced non-desensitizing inward currents were not affected by tetrodotoxin, a voltage-gated Na + channel blocker, 6-cyano-7-nitro-quinoxaline-2,3-dione, a non- N -methyl-D-aspartate (NMDA) glutamate receptor antagonist and DL-2-amino-5-phosphonopentanoic acid, an NMDA receptor antagonist. (kjpp.net)

These highlights do not include all the information needed to use EXTENDED PHENYTOIN SODIUM CAPSULES safely and effectively. (nih.gov)
Extended phenytoin sodium capsules are indicated for the treatment of tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery. (nih.gov)
Adult starting dose in patients who have received no previous treatment is one 100 mg extended phenytoin sodium capsule three times a day, with dose adjustments as necessary. (nih.gov)
Adult once-a-day dose: If seizure control is established with divided doses of three 100 mg extended phenytoin sodium capsules daily, once-a-day dosage with 300 mg extended phenytoin sodium capsules may be considered. (nih.gov)
Extended phenytoin sodium capsules are available as 100 mg extended phenytoin sodium capsules. (nih.gov)
Discontinue phenytoin sodium at the first sign of a rash, unless the rash is clearly not drug-related. (nih.gov)
Cases of acute hepatotoxicity have been reported with phenytoin sodium. (nih.gov)
The rate of intravenous fosphenytoin sodium injection administration should not exceed 150 mg phenytoin sodium equivalents (PE) per minute in adults and 2 mg PE/kg/min (or 150 mg PE/min, whichever is slower) in pediatric patients because of the risk of severe hypotension and cardiac arrhythmias. (nih.gov)

Marine toxins have potent actions on diverse sodium ion channels regulated by transmembrane voltage (voltage-gated ion channels) or by neurotransmitters (nicotinic acetylcholine receptor channels). (mdpi.com)
DOHMH's for sodium channel toxins to provide a semiquantitative mea- investigation revealed that 13 persons became ill after eating sure of composite ciguatoxicity in fish ( 1 ). (cdc.gov)

Riluzole preferentially blocks TTX -sensitive sodium channels , which are associated with damaged neurons . (curecrowd.com)
Their in-vitro electrophysiological analysis is excellent, showing full selectivity profiles (including difficult to work with channels such as hNav1.8 and hNav1.9) from HEK293 cells and also showing inhibition of the TTX-S current with both mouse and human cultured DRG neurons. (elifesciences.org)
Voltage-gated sodium channels initiate action potentials in brain neurons, and sodium channel blockers are used in therapy of epilepsy. (xcessbio.com)
The upregulation of voltage-gated sodium channel Na v 1.3 has been linked to hyperexcitability of axotomized dorsal root ganglion (DRG) neurons, which underlies neuropathic pain. (jneurosci.org)

The effects of the novel analogs were tested on sodium currents of native myofibers. (uniba.it)

Drosophila Sodium Channel 1 (DSC1) was predicted to encode a sodium channel based on a high sequence similarity with vertebrate and invertebrate sodium channel genes. (duke.edu)

Our study shows that DSC1 encodes a voltage-gated cation channel similar to the BSC1 channel in B. germanica. (duke.edu)
Protoxin II (ProTx II) is a high affinity gating modifier that is thought to selectively block the Na v 1.7 voltage-dependent Na + channel, a major therapeutic target for the control of pain. (smartox-biotech.com)
Sig1R-modulatory activity was first found for phenytoin, an anticonvulsant drug that primarily acts by blocking the voltage-gated sodium channels. (frontiersin.org)
The targets that many researchers are aiming at are called voltage-gated sodium ion channels, which are common in pain-sensing nerve cells. (scientificamerican.com)
Certain venom components have just the right shape and chemical activity to latch onto a part of the channel called a voltage sensor, and that action shuts the channel. (scientificamerican.com)
The voltage gated sodium channel Na V 1.8 has been postulated to play a key role in the transmission of pain signals. (ncl.ac.uk)
Opening these channels hyperpolarizes the smooth muscle, which closes voltage-gated calcium channels and decreases intracellular calcium. (cvpharmacology.com)
Voltage-gated sodium channels are fundamental in the generation and transmission of painful signals. (elifesciences.org)
The activation of CatSper by progesterone and prostaglandins, as well as the ligand-independent regulation of the channel by a change in the membrane voltage and intracellular pH are going to be addressed. (123dok.net)
Voltage-gated sodium channels mediate a rapid and transient increase in Na + permeability in response to membrane depolarization, thereby contributing to the generation and conduction of action potentials. (jneurosci.org)

The upstroke of the action potential in myocytes is mediated by sodium - thus alteration of sodium flux has the most potent effect on ventricular arrhythmias. (gpnotebook.com)

Lidocaine, like cocaine, is a local anesthetic with potent effects as a sodium-channel blocker. (digglicious.com)

Though spreading depolarizations are notoriously difficult to block, terminal depolarization onset was delayed by dibucaine, a local amide anesthetic and sodium channel blocker. (openrepository.com)

Rather, its potent glutamate uptake activator activity seems to mediate many of its effects. (curecrowd.com)

Calcitonin gene-related peptide (CGRP) is a potent vasodilator and is a key neuropeptide that is thought to be a central component of headache pathophysiology. (medscape.com)
The potent vasodilator actions of minoxidil can lead to fluid retention and edema formation. (cvpharmacology.com)

Recent evidence suggests that amiloride, a potent and nonselective blocker of acid-sensing ion channels, suppresses generalized seizures induced by maximal electroshock and pentylenetrazole. (nih.gov)
These findings suggest that amiloride may modulate seizure generation and propagation, probably via mechanisms involving acid-sensing ion channels in the pilocarpine model of temporal lobe epilepsy. (nih.gov)
In congestive heart failure, Amiloride Hydrochloride may be effective alone, but its principal indication is for concomitant use in patients receiving thiazides or more potent diuretic agents. (janusinfo.se)

Displays 100-fold selectivity over other sodium channel subtypes. (tocris.com)
However, BSC1, a DSC1 ortholog in Blattella germanica, was recently shown to encode a cation channel with ion selectivity toward Ca(2+). (duke.edu)

We hypothesized that the combination of potent transient receptor potential vanilloid type 1 agonist resiniferatoxin (RTX) and selected antidepressants (amitriptyline, doxepin, and fluoxetine, also potent sodium channel blockers) would produce prolonged and predominantly sensory nerve block. (metajournal.com)

ProTx II is a selective Na V 1.7 channel blocker. (tocris.com)
ATTO488-ProTx-II is a fluorescently labeled ProTx-II , a famous Na v 1.7 blocker. (smartox-biotech.com)
We aimed at producing ProTx II analogues entitled with novel functionalities for cell distribution studies and biochemical characterization of its Na v channel targets. (smartox-biotech.com)
Two of the produced ProTx II analogues, Biot-ProTx II and ATTO488-ProTx II, best emulate the pharmacological properties of unlabelled ProTx II, whereas other analogues remain high affinity blockers of Na v 1.7. (smartox-biotech.com)
The biotinylated version of ProTx II efficiently works for the pull-down of several Na v isoforms tested in a concentration-dependent manner, whereas the fluorescent ATTO488-ProTx II specifically labels the Na v 1.7 channel over other Na v isoforms tested in various experimental conditions. (smartox-biotech.com)
The properties of these ProTx II analogues as tools for Na v channel purification and cell distribution studies pave the way for a better understanding of ProTx II channel receptors in pain and their pathophysiological implications in sensory neuronal processing. (smartox-biotech.com)

They are used with a beta-blocker and diuretic to attenuate the reflex tachycardia and retention of sodium and fluid, respectively. (cvpharmacology.com)
Sodium removal-by dietary salt restriction and a diuretic-is the mainstay in management of symptomatic heart failure, especially if edema is present. (brainkart.com)

E)-Cardamonin CAS No. : 19309-14-9 Biological Activity：(E)-Cardamonin ((E)-Cardamomin) is a novel antagonist of hTRPA1 cation channel with an IC50 of 454 nM. (epigenetics-modulation-frontier.com)
Fulvestrant CAS No. : 129453-61-8 Biological Activity：Fulvestrant (ICI 182780) is a pure antiestrogen and a potent estrogen receptor (ER) antagonist with an IC50 of 9.4 nM. (epigenetics-modulation-frontier.com)

Class I drugs are sodium channel blockers (membrane-stabilizing drugs) that block fast sodium channels, slowing conduction in fast-channel tissues (working atrial and ventricular myocytes, His-Purkinje system). (msdmanuals.com)

Azilsartan CAS No. : 147403-03-0 Biological Activity：Azilsartan (TAK-536) is an orally active, potent, selective and specific angiotensin II type 1 receptor (AT1) antagonist. (epigenetics-modulation-frontier.com)

The transporters mediate the simultaneous efflux of a hydrogen ion and the influx of a sodium ion across the plasma membrane, the driving force being the inwardly directed electrochemical Na + gradient. (tocris.com)
The sperm-specific ion channel CatSper is the principal calcium channel in sperm mediating the calcium influx into the sperm flagellum and acting as an essential modulator of downstream mechanisms involved in fertilization. (123dok.net)

Fortuitously, the mambalgins have no effect on most other ion channels, which may explain why mice injected with the substances had no apparent side effects. (scientificamerican.com)

The transient receptor potential (TRP)A1 receptor is part of a larger family of TRP ion channels that includes TRPV, TRPM, TRPC, TRPN, TRPP, and TRPML [ 1 - 3 ]. (biomedcentral.com)

Scholars@Duke publication: Molecular characterization and functional expression of the DSC1 channel. (duke.edu)
Extensive alternative splicing and RNA editing of the DSC1 transcripts suggest the molecular and functional diversity of the DSC1 channel. (duke.edu)

Cawthron Institute has announced they have developed a reliable and commercially scalable method for producing neosaxitoxin , a potent toxin from the paralytic shellfish toxin family, that can be combined with existing local anaesthetics for use as a local anaesthetic during and after surgery in post-operative patients. (aquahoy.com)
The Chondrodendron tomentosum plant produces tubocurarine, a potent toxin used to create poisoned arrows. (labonline.com.au)

These channels are quite different in terms of structure, sequence and function and both have been regarded as important targets for drugs aimed at treating atrial fibrillation. (frontiersin.org)
Even when plants themselves don't produce a useful compound, they often have chemicals that inspire more potent synthetic drugs. (labonline.com.au)
The Amazon is home to unique wildlife that contains potent compounds that scientists can use to synthesise new drugs. (labonline.com.au)
Class IV drugs are the nondihydropyridine calcium channel blockers, which depress calcium-dependent action potentials in slow-channel tissues and thus decrease the rate of automaticity, slow conduction velocity, and prolong refractoriness. (msdmanuals.com)

Sodium nitrite in the drinking water at levels of 10.0, 100.0 and 400.0 maximum admissible concentration accelerated the development of Rauscher Leukemia virus-induced leukemia in mice. (cancerprev.org)
This review aims to provide insights into the structure, localization, and function of the mammalian CatSper channel, primarily human and mice. (123dok.net)

To our knowledge, the new compounds are the most potent Mex-like Nav blockers obtained to date and deserve further investigation. (uniba.it)

Prilocaine acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. (digglicious.com)

The compound, dubbed cVc1.1, turned out to be 100 times more potent than gabapentin, a common treatment for nerve pain. (scientificamerican.com)
The Kv1.3 channel has become a therapeutic target for the treatment of various diseases. (mdpi.com)
Fosphenytoin sodium injection, USP is indicated for the treatment of generalized tonic-clonic status epilepticus and prevention and treatment of seizures occurring during neurosurgery. (nih.gov)

Snake venom is also a source of selective channel blockers. (scientificamerican.com)

In order to illustrate the potential of the updated Geomfinder version, we show a case of use in which similar 3D patterns were detected in the cardiac ions channels NaV1.5 and TASK-1. (frontiersin.org)

Like the BSC1 channel, all three functional DSC1 channels are permeable to Ca(2+) and Ba(2+), and also to Na(+) in the absence of external Ca(2+). (duke.edu)

The antiarrhythmic actions are mediated through effects on sodium channels in Purkinje fibers. (digglicious.com)
The kinetics of sodium channel blockade determine the heart rates at which their electrophysiologic effects become manifest. (msdmanuals.com)
Trials of β -blocker therapy in patients with heart failure are based on the hypothesis that excessive tachycardia and adverse effects of high catecholamine levels on the heart contribute to the down-ward course of heart failure. (brainkart.com)

The mambalgins, as the molecules are called, plug a particular set of acid-sensing ion channels in peripheral nerve cells that, like sodium channels, help the cells send pain signals. (scientificamerican.com)

Calcium channel blockers verapamil, nifedipine, diltiazem and isradipine arrested basic fibroblast growth factor induced human umbilical arterial endothelial cell proliferation. (cancerprev.org)

Previously identified potent and/or use-dependent mexiletine (Mex) analogs were used as template for the rational design of new Nav-channel blockers. (uniba.it)
For this task, they develop a computational workflow that is based on in silico manipulations of the interaction of ProTxII with a Na channel structure determined previously and evaluation of the predicted mutations with electrophysiology. (elifesciences.org)

Being the most potent sodium channel blocker among its group, it causes severe cardiotoxicity (eg, wide QRS complex, hypotension) without producing significant antimuscarinic symptoms. (medscape.com)

Sodium-hydrogen exchangers (Na + /H + exchangers, NHE) are ATP-independent membrane glycoprotein transporters that are involved in the regulation of intracellular pH, cell volume and the cellular response to hormones and mitogens. (tocris.com)

This uncontrolled release is due to a defective calcium channel in the sarcoplasmic reticulum, known as ryanodine receptor 1 (RyR1). (medscape.com)

We hope that the current analysis will be a useful resource for researchers and provide glimpse of direction toward the design and development of more specific, selective, and potent Src kinase inhibitors. (bvsalud.org)

Contactin/F3, a cell adhesion molecule, has been shown to interact with and enhance surface expression of sodium channels Na v 1.2 and Na v 1.9. (jneurosci.org)

Irbesartan CAS No. : 138402-11-6 Biological Activity：Irbesartan (SR-47436) is an orally active Ang II type 1 (AT1) receptor blocker (ARB). (epigenetics-modulation-frontier.com)

Anatomy24

Organisms14

Diseases12

Chemicals and Drugs166

Analytical, Diagnostic and Therapeutic Techniques and Equipment10

Psychiatry and Psychology1

Phenomena and Processes27

Disciplines and Occupations2

Technology, Industry, Agriculture1

Information Science2

Beta-blockers3

NaV1.77

Peptides2

Potassium8

Tetrodotoxin3

Phenytoin sodium8

Toxins2

Neurons4

Currents1

Vertebrate1

Voltage10

Arrhythmias1

Lidocaine1

Anesthetic1

Glutamate1

Vasodilator2

Amiloride3

Selectivity2

Predominantly1

ProTx II6

Diuretic2

IC502

Ventricular1

Antagonist1

Influx2

Substances1

Transient1

Molecular2

Toxin2

Drugs4

Mice2

Compounds1

Propagation1

Treatment3

Venom1

NaV1.51

Permeable1

Effects3

Acid-sensing ion1

Arterial1

Previously2

Severe1

Intracellular1

Calcium channel1

Specific1

Expression1

Type1