Ion channel blockers

Maintenance of electrical potential between the cell membrane exterior and interior is a necessity for the proper functioning of excitable neuronal and muscle cells. Chemical compounds can disturb ion fluxes that are essential for the maintenance of the membrane potentials. Fluxes of ions into the cells or out of the cells can be blocked by ion channel blockers (for example, some marine tox-... 

Figure 16.9 Ion channel blockers from virtual screening.

A growing number of other diverse compounds have also been shown to bind to an allosteric site on the muscarinic receptors. Among them are pirenzepine (highly selective for Mi receptor), lidocaine and verapamil (ion channel blockers), tacrine (anticholinesterase compound), batrachotoxin, and strychnine (glycine receptor antagonist) [25,31-35],... 

Park, K.H., Chhowalla, M., Iqbal, Z., and Sesti, F. (2003) Single-walled carbon nanotubes are a new class of ion channel blockers./. Biol. Chem. 278, 50212-50216. 

The limited success of highly specific drugs that target single ion channels and the efficacy of multi-ion channel blockers such as amiodarone has shifted the emphasis in antiarrhythmic drug development to the multi-ion channel blockers class of drugs. Vernakalant is an investigational multi-channel blocker that was developed for the treatment of atrial fibrillation. 

Carter, A. J., Bechtel, W. D., Grauert, M., Harrison, P., Merz, H., Stransky, W. Bill 277 CL is a potent and specific ion-channel blocker of the NMDA receptor-channel complex, J. Pharmacol. Exp. Ther. 1995, 275, 1382-1389. 

Tutdibi, O., Brinkmeier, H., Rudel, R., and Fohr, K.J., 1999, Increased calcium entry into dystrophin-deficient muscle fibres of MDX and ADR-MDX mice is reduced by ion channel blockers, J Physiol, 515 ( Pt 3), pp 859-868. 

Traditional treatment of epilepsy involves anticonvulsants to block excitatory transmission. The majority of these antiepileptic drugs are known ion channel blockers [for a summary see Gourfin-kel-An et al. (2004)] More drastic approaches involve surgical removal of the epileptic foci. Gene therapy approaches attempt to block excitation by blocking gene expression (Xiao et al., 1997 Haberman et al., 2002) of excitatory neurotransmitters or by overexpression of the genes involved in inhibition of excitation (Haberman et al., 2003 Lin et al., 2003 Richichi et al., 2004). 

Development of the NMDA Ion-Channel Blocker, Aptiganel Hydrochloride, as a Neuroprotective Agent for Acute CNS Injury... 

Tikosyn Dofetilide 125, 250, 500 (jig Capsule Maintenance of normal sinus rhythm and conversion of atrial fibrillation/ flutter Cardiac ion channel blocker/ antiarrhythmic drug MCC, corn starch, silicon dioxide, magnesium stearate Pfizer... 

Similarly, hypothermia has known effects on cardiac rhythm, electrolyte balance, and metabolism, all of which could be enhanced when combined with pharmaceutical agents such as calcium or other ion channel blockers. Thus, as with all possible treatments, there is the potential not only for improvement, but also significant harm if an inappropriate combination is employed. 

Wohlrab D, Markwardt F (1999) Influence of ion channel blockers on proliferation and free intracellular Ca2+ concentration of human keratinocytes. Skin Pharmacol Appl Skin Physiol 12 257-265... 

Tao, H. et al. 2006. Efficient characterization of use-dependent ion channel blockers by real-time monitoring of channel state. Assay Drug Dev. Technol. 4, 57-64. 

The noncompetitive NMDA antagonist ion channel blockers such as PCP (148) and the competitive antagonists such as CGS 19755 (149) are both psychotomimetic in humans... 

The bispidine backbone (bispidine= 3,7-diazabicyclo[3.3.1]nonane) I is a simplified derivative of the natural product sparteine, 2 (see Chart 1 shown is the structure of a-isosparteine). Sparteine, a polycyclic alkaloid, occurs in a wide range of plants and has a variety of medical and chemical applications. It has been investigated extensively, for example, as a cardiac antiarrhyfhmia (1, 2), an ion channel blocker (3,4), and an uterotonic dmg (5). It was also used as a chiral base... 

An apparent common structural theme is hardly visible in these ion channel blocker, but most of these alkaloids have a tertiary nitrogen, which is protonated under physiological conditions, are relatively large and bulky molecules which contain many functional groups, so that various interactions become possible with amino acid residues of the channel proteins [66]. 

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