K-channel blocker

Aronov AM, Goldman BB. A model for identifying HERG K+ channel blockers. Bioorg Med Chem 2004 12 2307-37. 

Cavalli A, Poluzzi E, De Ponti F, Recanatini M. Toward a pharmacophore for drugs inducing the long QT syndrome insights from a CoMFA study of HERG K channel blockers. / Med Chem 2002 45 3844-53. 

Covalent labelling of these two polypeptides was also specifically blocked by other PCP analogues such as TCP, by some K channel blockers (4 - A P and tetrabutylammoni urn ions), and stereoselectively by certain PCP-like "sigma opiates" (dexoxadrol levoxadrol)... 

There is ample precedent for a modulatory role of K channels in behavior. The K channel blocker, 4-AP, selectively blocks component T (Bartschat and Blaustein 1985a). prolongs nerve action potentials, and enhances neurotransmitter release (Llinas et al. 1975). In man, intoxication with this agent may lead to dissociative behavior, agitation, confusion, convulsions, and coma (Spyker et al. 1980). However, the behavioral aberrations induced by 4-AP differ qualitatively from those induced by PCP. This implies that block of various types of presynaptic K channels may modify behavior and mental activity however, the precise nature of the behavioral manifestations is likely to depend upon the specific type of K channel that is affected. 

Brading What is the role of the action potentials in generating contraction This is not entirely clear. We know in strips that if we add iberiotoxin or any K+ channel blockers we do get contractions. But the frequency of contractions is nothing like the frequency of the action potentials. 

Galanakis D, Davis CA, Del Rey Herrero B, Ganellin CR, Dunn PM, Jenkinson DH. Synthesis and structure-activity relationships of dequalinium analogues as K(+) channel blockers. Investigations on the role of the charged heterocycle. J Med Chem 1995 38 595-606. 

Yarishkin OV, Ryu HW, Park JY, Yang MS, Hong SG, Park KH. 2008. Sulfonate chalcone as new class voltage-dependent K + channel blocker. Bioorg Med Chem Lett 18 137-140. 

Ghisdal, P., and Morel, N. 2001. Cellular target of voltage and calcium-dependent K+ channel blockers involved in EDHF-mediated responses in rat superior mesenteric artery. Br. J. Pharmacol. 134 1021-1028. 

Type II diabetes Stimulating the release of insulin from the pancreas. ATP-dependent K-channel blocker Calcium hydrogen phosphate, MCC, maize starch, polacrilin, potassium, povidone, glycerol (85%), magnesium stearate, meglumine, poloxamer Novo Nordisk... 

The spinal antinociceptive effect of DPDPE is blocked totally by a small conductance Ca2 + -activated K + channel blocker apamin [109]. The DPDPE-induced spinal antinociception is not inhibited by a ATP-sensitive K + channel blocker glyburide [109], Like morphine, tetraethylammonium, 4-aminopyridine, and charybdotoxin are unable to block the effects of DPDPE [109], These findings suggest that the modulation of apamin-sensitive K + channels appears to play a role in the DPDPE-induced antinociception in the spinal cord. 

BmP07, K+ channel blocker from scorpion B. martensii Karsch BmBKTxl, K+ channel blocker from B. martensii Karsch BmKX, K+ channel blocker from B. martensii Karsch... 

Table 1 summarizes the available data on the effects of K+ channel blockers and activators on cell proliferation. 

On the other hand, a given K+ channel may well express in multiple cancer cells of distinct histological origins therefore even a relatively specific K+ channel blocker might inhibit proliferation of several distinct cells. For instance, cisapride can inhibit proliferation of breast cancer cells, neuroblastoma cells, gastric cancer cells, etc., simply because HERG is ubiquitously expressed in human tissues. 

Lang RJ, Zhang Y (1996) The effects of K+channel blockers on the spontaneous electrical and contractile activity in the proximal renal pelvis of the guinea pig. J Urol 155 332-336... 

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