Sodium channels voltage-sensitive

Brevetoxins Unique Activators of Voltage-Sensitive Sodium Channels... 

Research in this area advanced in the 1970 s as several groups reported the isolation of potent toxins from P. brevis cell cultures (2-7). To date, the structures of at least eight active neurotoxins have been elucidated (PbTx-1 through PbTx-8) (8). Early studies of toxic fractions indicated diverse pathophysiological effects in vivo as well as in a number of nerve and muscle tissue preparations (reviewed in 9-11). The site of action of two major brevetoxins, PbTx-2 and PbTx-3, has been shown to be the voltage-sensitive sodium channel (8,12). These compounds bind to a specific receptor site on the channel complex where they cause persistent activation, increased Na flux, and subsequent depolarization of excitable cells at resting... 

Catterall, W. A. Molecular properties of voltage-sensitive sodium channels. Annu. Rev. Biochem. 55, 953-985,1986. 

It blocks voltage-sensitive sodium channels, modulates the voltage-activated Ca currents, and increases potassium conductance. 

Zonisamide is a broad-spectrum sulfonamide AED that blocks voltage-sensitive sodium channels by reducing voltage-dependent T-type Ca channels it also weakly inhibits carbonic anhydrase, and inhibits glutamate release. 

Neurotransmitter release induced by potassium-dependent depolarization is a physiologically relevant way to investigate pyrethroid effects on calcium-dependent neurotransmitter release since this process is independent of voltage-sensitive sodium channels [71]. Furthermore, potassium-stimulated calcium influx and subsequent neurotransmitter release by synaptosomes is blocked by a variety of voltage-sensitive calcium channel antagonists but not by TTX [4, 71, 72]. 

As previously mentioned, early in vivo acute toxicity studies indicated that the action of Type II pyrethroids on the nervous system was different from that of the Type I pyrethroids. Deltamethrin decreased the acetylcholine content of the cerebellum, whereas DDT, a well-established voltage-sensitive sodium channel agonist, and cismethrin, caused no significant reduction [2]. 

Brown GB, Gaupp JE, Olsen RW (1988) Pyrethroid insecticides stereospecific allosteric interaction with the batrachotoxinin-a benzoate binding site of mammalian voltage-sensitive sodium channels. Mol Pharmacol 34 54-59... 

Poli MA, Mende TJ, Baden DG (1989) Brevetoxins, unique activators of voltage-sensitive sodium channels, bind to specific sites in rat brain synaptosomes. Mol Pharmacol 30 129-135 Pullaiah KC, Surapaneni RK, Rao CB, Albizati KF, Sullivan BW, Faulkner DJ, He CH, Clardy J (1985) Dictyoxetane, a novel diterpene from the brown alga Dictyota dichotoma from the Indian Ocean. J Org Chem 50 3665-3666... 

Carbamazepine exerts its anticonvulsant activity through its own action on voltage sensitive sodium channels and those of its relatively stable 10-11-epoxide. The compound shows a number of potential toxicities including skin rash, hepatic necrosis and teratogenicity. It is possible the 10-11-epoxide is the causative agent, but struc-... 

The ditetrazolium salts (309) have been patented for use in electrochromic electrodes which are used in display devices <89JAP01230026) and tetrazolium salts have also been developed for cell bioassays for neurotoxins active on voltage-sensitive sodium channels <93MI 417-03). Tests for inhibition of corrosion of zinc and brass carried out on 5-aminotetrazole showed it to be ineffective relative to other azoles <86MI 417-01). A number of tetrazoles including the 5-amino, 5-methyl, and 5-phenyl derivatives have been separately incorporated into surfactants used for corrosion inhibition with copper in water <9lMl4l7-07). Photopolymerizable resin compositions which are highly resistant... 

Mechanism of Action An anticonvulsant whose exact mechanism is unknown. May block voltage-sensitive sodium channels, thus stabilizing neuronal membranes and regulating presynaptic transmitter release of excitatory amino acids. Therapeutic Effect Reduces seizure activity... 

It is a keto analog of carbamazepine. It produces blockade of voltage sensitive sodium channels, leading to stabilisation of hyperexcited neural membranes, inhibition of repetitive neuronal firing and diminution of propagation of synaptic impulses. 

It is phenyltriazine compound, chemically unrelated to existing antiepileptic drugs. It acts primarily via a dose dependent blockade of voltage sensitive sodium channels in their slow inactivated state, thus stabilizing the presynaptic neuronal membrane inhibiting release of excitatory neurotransmitters mainly glutamate. 

Richardson, P. J., Mizuguchi, K., Jackson, A. P. Beta3 an additional auxiliary subunit of the voltage-sensitive sodium channel that modulates channels gating with distinct kinetics, Proc. Natl. Acad. Sci. USA 2000, 97, 2308-2313. 

In two children with cranial diabetes insipidus, desmopressin requirements fell while they were taking lamotrigine (590). Lamotrigine may act at voltage-sensitive sodium channels and reduce calcium conductance. Both of these mechanisms of action are shared by carbamaze-pine, which can cause hyponatremia secondary to inappropriate secretion of antidiuretic hormone. 

Sato C et al (2001) The voltage-sensitive sodium channel is a bell-shaped molecule with several cavities. Nature 409 1047-1051... 

Release of acetylcholine When an action potential propagated by the action of voltage-sensitive sodium channels arrives at a nerve ending, voltage-sensitive calcium channels in the presynaptic membrane open, causing an increase in the concentration of intracellular calcium. Elevated calcium levels promote the fusion of synaptic vesicles with the cell membrane and release of acetylcholine into the synapse. This release is blocked by botulinum toxin. By contrast, black widow spider venom causes all of the cellular acetylcholine stored in synaptic vesicles to spill into the synaptic gap. 

Anticonvulsant, antineuralgic for chronic pain, voltage-sensitive sodium channel antagonist... 

Acts as a use-dependent blocker of voltage-sensitive sodium channels... 

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