(f) 62 1-Heptanol

Figure 19 Structure of (a) GYKI-16638: combined class 1b and 3 actions, (b) BRL-32872: combined class 3 and 4 actions, (c-d) ranolazine and EGIS-7229: combined class 1, 3, and 4 actions, and (e-f) gap junction blockers: 16-doxyl-stearic acid and 1-heptanol.

BRL-32872 inhibits ischemia induced ventricular arrhythmias in minipigs, and it also reduces electrically induced VT in dogs. Moreover, it did not induce arrhythmias in rabbits, unlike selective IKr blockers. Combined class 1, 3, and 4 actions

The antianginal agent ranolazine (59) is an inhibitor of fatty acid oxidation having direct electrophysiological actions due to combined channel blockade of Na+, K+, and Ca2 + channels. It prolongs cardiac action potential duration without any rate dependency or induction of torsades. Interestingly, it suppresses drug-induced proarrhythmias induced by drugs that decrease IKr or increase the late sodium current.33

EGIS-7229 (60) is another novel compound with combined class 1, 3, and 4 actions. Low concentration of EGIS-7229 inhibits IKr and prolongs action potentials, but at higher concentrations it shortens action potentials with use-dependent inhibition of Na+ channels.34 Although the effects of EGIS-7229 are complex, it inhibits early after-depolarization, unlike sotatol which increases early after-depolarizations (EADs) in rabbit papillary muscles. Therefore, EGIS-7229, like BRL-32872, may have self-limiting action potential prolonging effects.

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