Potassium channel inhibition

CoMSIA (comparative molecular similarity index analysis) is a recent development from CoMFA and does not suffer from the alignment problem. It has been used to model hERG potassium channel inhibition by drugs [59] and the toxicity of phenylsulfonyl carboxylates [60], organophosphates [61], and polybrominated diphenyl ethers [62], with results comparable to those from CoMFA. 

Dearden JC, Netzeva TI. QSAR modelling of hERG potassium channel inhibition with low-dimensional descriptors. I Pharm Pharmacol 2004 56 Suppl S-82. 

Pearlstein RA, Vaz Rl, Kang J, Chen X-L, Preobrazhenskaya M, Shchekotikhin AE et al. Characterisation of HERG Potassium channel inhibition using COMSiA 3D QSAR and homology modeling approaches. Bioorg Med Chem Lett 2003 13 1829-35. 

Ekins, S., Balakin, K.V., Savchuk, N. and Ivanenkov, Y. (2006) Insights for human efher-a-go-go-related gene potassium channel inhibition using recursive partitioning and Kohonen and Sammon mapping techniques. Journal of Medicinal Chemistry, 49,... 

Lysenkova, L.N., Miroshnikova, O.V., Hendrix, J., and Rampe, D. Characterization of H ERG potassium channel inhibition using CoMSiA 3D QSAR and homology modeling approaches. Bioorg. Med. Chem. Lett. 2003, 13, 1829-1835. 

Dorn, A., Hermann, F., Ebneth, A., Bothmann, H., Trube, G., Christensen, K. and Apfel, C. (2005) Evaluation of a high-throughput fluorescence assay method for hERG potassium channel inhibition. Journal of Biomolecular Screening, 10, 339-347. 

Muscarinic M2 Myocardium, smooth muscle, some presynaptic sites CNS neurons Opening of potassium channels, inhibition of adenylyl cyclase... 

Using a variety of cell lines, D2R has been shown to couple to numerous G-proteins including Got i, Gai2, Gai3, Ga0 and Gaz. Depending on the cell type and isoform expressed, D2R activation can lead to the inhibition of AC and cAMP production, activation of potassium channels, inhibition of L-type calcium channels, stimulation of PLC activity and calcium mobilization, potentiation of Ca2+-evoked arachidonic acid release, stimulation of Na+/H+ exchange, and regulation of PI hydrolysis (Di Marzo et al., 1993 Mercier et al., 2001). 

Kirsch GE, Trepakova ES, Brimecombe JC, et al. Variability in the measurement of hERG potassium channel inhibition Effects of temperature and stimulus pattern. / Pharmacol Toxicol Methods. 2004 50(2) 93-101. 

This drug binds to both sodium and potassium channels, inhibiting recovery after repolarization of the membrane. 

Kim Y, Ma A-G, Kitta K, Fitch SN, Ikeda T, fiiara Y, Simon AR, Evans T, Suzuki Y (2003) Anthracycline-induced suppression of GATA-4 transcription factor implication in the regulation of cardiac myocyte apoptosis. Mol Pharmacol 63 368-377 Kirsch GE, Trepakova ES, Brimecombe JC, Sidach SS, Erickson HD, Kochan MC, Shyjka LM, Lacerda AE, Brown AM (2004) Variability in the measurement of hERG potassium channel inhibition Effect of temperature and stimulus pattern. J Pharmacol Method 50 93-101 Koury SI, Stone CK, Thomas SH (1996) Amrinone as an antidote in experimental verapamil overdose. Acad Emerg Med 3 762-767... 

Fox AJ, Barnes PJ, Urban L, Dray A (1993) An in vitro study of the properties of single vagal afferents innervating guinea-pig airways. J Physiol (Lond) 469 21-35 Fox AJ, Barnes PJ, Venkatesan P, Belvisi MG (1997) Activation of large conductance potassium channels inhibits the afferent and efferent function of airway sensory nerves in the Guinea pig. JChn Invest 99 513-519... 

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