Antiarrhythmic peptides

Until that point the mechanism of action of the peptide remained unclear. The first investigation directed toward the elucidation of the underlying mechanism of action revealed that the antiarrhythmic peptide did not alter depolar-... 

Fig. 22. Reduction in dispersion of the ventricular action potential duration by the synthetic antiarrhythmic peptide AAP10. The distribution of the action potential duration (assessed as the epicardial activation-recovery interval, ARI) on the surf ace of an isolated rabbit heart before and after treatment with AAP10. Note the greater variability of the epicardial action potential duration (ARI) before administration of AAP10 [Dhein et al., 1997c]. 

For the problem of prophylactic antiarrhythmic treatment these antiarrhythmic peptides are probably not the final solution. Because of their peptide nature they are not well suited for in vivo studies and they are probably only indicated for the prevention of arrhythmias due to reduced coupling, but they are a first step in the direction of a new class of drugs influencing gap junctional coupling. 

Aonuma S, Kohama Y, Akai K, Iwasaki S Studies on heart. XX. Further effect of bovine ventricle protein (BVP) and antiarrhythmic peptide (AAP) on myocardial cells in culture. Chem Pharm Bull (Tokyo) 1980a 28 3340-3346. 

Aonuma S, Kohama Y, Makino T, Fujisawa Y Studies on heart XXI. Amino acid sequence of antiarrhythmic peptide isolated from bovine atria. J Pharmacobiol Dyn 1982 5 40-48. 

Argentieri T, Cantor E, Wiggins JR Antiarrhythmic peptide has no direct cardiac actions. Experientia 1989 45 737-738. 

Dhein S, Manicone N, Muller A, Gerwin R, Ziskoven U, Irankhahi A, Minke C, Klaus W A new synthetic antiarrhythmic peptide reduces dispersion of epicardial activation recovery interval and diminishes alterations of epicardial activation patterns induced by regional ischemia. A mapping study. Naunyn Schmiedebergs Arch Pharmacol 1994 350 174-184. 

Dhein S, Gottwald M, Schafer T, Muller A, Gover R, Tudyka T Improvement of intercellular coupling by an antiarrhythmic peptide during ischemia and hypoxia. Eur Heart J 1997 18(suppl) 568. 

Dhein S, Schott M, Gottwald E, Tudyka T, Rutten P Antiarrhythmic effects of the antiarrhythmic peptide AAP10 in regional ischemia preservation of longitudinal propagation of activation. Circulation... 

Dhein S, Schott M, Tudyka T, Piecha D, Gottwald E, Klaus W Antiarrhythmic peptides A new antiarrhythmic principle. Exp Clin Cardiol 1997c 2 51-58. 

Dhein S, Tudyka T Therapeutic potential of antiarrhythmic peptides. Cellular coupling as a new antiarrhythmic target. Drugs 1995 49 851-855. 

Dhein S, Tudyka T, Schott M, Gottwald E, Miiller A, Klaus W A new antiarrhythmic peptide improves cellular coupling A possible new antiarrhythmic mechanism. Circulation 1995b 92(suppll) 641. 

Gottwald M, Gottwald E, Dhein S Increased dispersion of epicardial potential duration caused by PMN s is decreased by diminishing cellular uncoupling A study with antiarrhythmic peptide and nordihydroguartic acid (abstract). Pflugers Arch 1997 433(suppl) 135. 

Kohama Y, Iwabuchi K, Shibahara T, Okabe M, Mimura T Response of immunoreactive antiarrhythmic peptide (IR-AAP) level associated with experimental arrhythmia in rats. J Pharmacobiodyn 1986 9 806-810. 

Kohama Y, Kawahara Y, Kabe M, Mimura T, Aonuma S Determnation of immunoreactive antiarrhythmic peptide (AAP) in rats. J Pharmacobiodyn 1985 8 1024-1031. 

Kohama Y, Okimoto N, Mimura T, Fukaya C, Watanabe M, Yokoyama K A new antiarrhythmic peptide, N-3-(4-hydroxyphenyl)-propionyl-Pro-Hyp-Gyl-Ala-Gly. Chem Pharm Bull 1987 35 3928-3930. 

Midler A, Gottwald M, Tudyka T, Linke W, Klaus W, Dhein S Increase in gap junction conduction by an antiarrhythmic peptide. Eur J Pharmacol 1997a 327 65-72. 

S. Weng, M. Lauven, T. Schaefer, L. Polontchouk, R. Grover, S. Dhein, Pharmacological modification of gap junction coupling by an antiarrhythmic peptide via protein kinase C activation, Faseb J16,1114-1116. 

Example 3 Plasma instability can be a major barrier to the therapeutic use of small peptides. Even with IV administration, peptidases stand ready to degrade these compounds through amide hydrolysis. This made in vivo use of an interesting series of antiarrhythmic peptides (AAPs) impractical. The hexapeptide AAPIO, shown in Figure 8.28, had a half-life of only... 

Haugan, K., et al. Gap junction-modifying antiarrhythmic peptides Therapeutic potential in atrial fibrillation. Drugs Future 2007, 32, 245-260. 

T.C. Clarke, D. Thomas, J.S. Petersen, W.H. Evans, P.E. Martin, The antiarrhythmic peptide rotigaptide (ZP123) increases gap junction intercellular communication in cardiac myocytes and HeLa cells expressing connexin 43, Br J Pharmacol 147 (2006) 486-495. 

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