Chiral separation of racemate CPU86017, an anti-arrhythmic agent, produces stereoisomers possessing favourable ion channel blockade and less α-adrenoceptor antagonism

Clinical and Experimental Pharmacology and Physiology

Volumn 35, Issue 5-6, 2008, Pages 643-650

  Li, Na ^a   Yang, Lin ^a   Dai, De Zai ^a   Wang, Qiu Juan ^a   Dai, Yin ^a  

^a CHINA PHARMACEUTICAL UNIVERSITY   (China)

Author keywords

Anti arrhythmic agents; CPU86017; IKr; IKs; Receptor operated calcium channels; Stereoisomer; Voltage dependent calcium channels

Indexed keywords

ALPHA ADRENERGIC RECEPTOR; ANTIARRHYTHMIC AGENT; CALCIUM; CALCIUM CHANNEL; CPU 86017; ION CHANNEL; PHENYLEPHRINE; POTASSIUM CHLORIDE; UNCLASSIFIED DRUG; VOLTAGE DEPENDENT CALCIUM CHANNEL;

ALPHA ADRENERGIC RECEPTOR BLOCKING; ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CALCIUM TRANSPORT; CHIRALITY; CONTROLLED STUDY; DRUG EFFICACY; DRUG POTENCY; GUINEA PIG; IC 50; ION CURRENT; MALE; NONHUMAN; PATCH CLAMP; SEPARATION TECHNIQUE; STEREOISOMERISM; VASCULAR RING; VASCULAR SMOOTH MUSCLE;

ADRENERGIC ALPHA-ANTAGONISTS; ANIMALS; ANTI-ARRHYTHMIA AGENTS; AORTA; BERBERINE; GUINEA PIGS; ION CHANNELS; MALE; MOLECULAR STRUCTURE; MYOCYTES, CARDIAC; RATS; VASOCONSTRICTION;

EID: 41749094257     PISSN: 03051870     EISSN: 14401681     Source Type: Journal    
DOI: 10.1111/j.1440-1681.2007.04854.x     Document Type: Article

References (40)

1. Kulig K, Nowicki P, Malawska B. Influence of the absolute configuration on pharmacological activity of antihypertensive and antiarrhythmic drugs. Pol. J. Pharmacol. 2004 56 : 499 508.
2. Rentsch KM. The importance of stereoselective determination of drugs in the clinical laboratory. Biochem. Biophys. Methods 2002 54 : 1 9.
3. + channels and their role in cardiac arrhythmias. Am. J. Med. 2001 110 : 50 9.
4. Keating MT, Sanguinetti MC. Molecular and cellular mechanisms of cardiac arrhythmias. Cell 2001 104 : 569 80.
5. Splawski I, Timothy KW, Decher N et al. Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc. Natl Acad. Sci. USA 2005 102 : 8089 96.
6. Waldo AL, Camm AJ, deRuyter H et al. Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators: Survival With Oral d-Sotalol. Lancet 1996 348 : 7 12.
7. Dai DZ. Two patterns of ion channelopathy in the myocardium: Perspectives for development of anti-arrhythmic agents. Curr. Opin. Invest. Drugs 2005 6 : 289 97.
8. Boriani G, Biffi M, Valzania C, Bronzetti G, Martignani C. Short QT syndrome and arrhythmogenic cardiac diseases in the young: The challenge of implantable cardioverter-defibrillator therapy for children. Eur. Heart J. 2006 27 : 2382 4.
9. + channel-mediated cardiac channelopathies. Methods Mol. Biol. 2006 337 : 167 83.
10. Stengl M, Ramakers C, Donker DW et al. Temporal patterns of electrical remodeling in canine ventricular hypertrophy: Focus on IKs downregulation and blunted beta-adrenergic activation. Cardiovasc. Res. 2006 72 : 90 100.
11. Salataa JJ, Selnickb HG, Lynch JJ. Pharmacological modulation of I(Ks): Potential for antiarrhythmic therapy. Curr. Med. Chem. 2004 11 : 29 44.
12. Volders PG, Stengl M, van Opstal JM et al. Probing the contribution of IKs to canine ventricular repolarization: Key role for beta-adrenergic receptor stimulation. Circulation 2003 107 : 2753 60.
13. Cui YJ, Yang P, Dai DZ. CPU-86017 supresses tachyarrhythmias induced by ouabain and myocardial infarction. Concentrations in plasma and different areas of the heart in dogs. Drug Dev. Res. 2003 58 : 131 7.
14. Na T, Huang ZJ, Dai DZ, Zhang Y, Dai Y. Abrupt changes in FKBP12.6 and SERCA2a expression contribute to sudden occurrence of ventricular fibrillation on reperfusion and are prevented by CPU86017. Acta Pharmacol. Sin. 2007 28 : 773 82.
15. Dai DZ. CPU86017: A novel Class III antiarrhythmic agent with multiple actions at ion channels. Drug Dev. Res. 2006 24 : 101 15.
16. Zhang TT, Cui B, Dai DZ, Tang XY. Pharmacological efficacy of CPU 86017 on hypoxic pulmonary hypertension in rats: Mediated by direct inhibition of calcium channels and antioxidant action, but indirect effects on the ET-1 pathway. J. Cardiovasc. Pharmacol. 2005 46 : 727 34.
17. Guan L, Yang TT, Zhang C, Dai DZ. Pharmacokinetic differences between CPU86017 and its chiral isomers in mice. Drug Dev. Res. 2005 66 : 230 (Abstract).
18. Zhang C, Lin Y, Hua WY. Synthesis of chiral compounds of 4-chlorobenzyl tetrahydroberberine chloride. J. Chin. Pharm. Univ. 2004 35 : 393 6 (in Chinese).
19. + currents in guinea-pig ventricular myocytes. J. Pharm. Pharmacol. 2000 52 : 403 8.
20. Satoh H. Modulation by nicotine of the ionic currents in guinea pig ventricular cardiomyocytes relatively higher sensitivity to IKR and IK1. Vas. Pharmacol. 2002 39 : 55 61.
21. Huang ZJ, Dai DZ, Li N, Na T, Ji M, Dai Y. Calcium antagonist property of CPU228, a dofetilide derivative, contributes to its low incidence of torsades de pointes in rabbits. Clin. Exp. Pharmacol. Physiol. 2007 34 : 310 17.
22. 2+. Acta Pharmacol. Sin. 1998 19 : 543 7.
23. Belus A, White E. Effects of streptomycin sulphate on ICa,L, IKR and IKS in guinea-pig ventricular myocytes. Eur. J. Pharmacol. 2002 445 : 171 8.
24. Witchel HJ. The hERG potassium channel as a therapeutic target. Expert Opin. 2007 11 : 1 16.
25. Siddoway LA. Amiodarone: Guidelines for use and monitoring. Am. Fam. Physician 2003 68 : 2189 96.
26. Dorian P, Borggrefe M, Al-Khalidi HR et al. Placebo-controlled, randomized clinical trial of azimilide for prevention of ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator. Circulation 2004 110 : 3646 54.
27. Lombardi F, Borggrefe M, Ruzyllo W, Luderitz B. Azimilide vs. placebo and sotalol for persistent atrial fibrillation: The A-COMET-II (Azimilide- CardiOversion MaintEnance Trial-II) trial. Eur. Heart J. 2006 27 : 2224 31.
28. Schimpf R, Wolpert C, Gaita F, Giustetto C, Borggrefe M. Short QT syndrome. Cardiovasc. Res. 2005 67 : 357 66.
29. Gaita F, Giustetto C, Bianchi F et al. Short QT syndrome: Pharmacological treatment. J. Am. Coll. Cardiol. 2004 43 : 1494 9.
30. Dai DZ, Hu HJ, Yang DM et al. Chronic levothyroxin treatment is associated with ion channel abnormalities in cardiac and neuronal cells. Clin. Exp. Pharmacol. Physiol. 1999 26 : 819 21.
31. Wang HL, Li SB, Dai DZ. Change in L-type calcium current in single guinea pig hypertrophic ventricular myocytes induced by levothyroxin. J. Chin. Pharm. Univ. 2000 31 : 130 4 (in Chinese).
32. + current in cardiomyocytes from hypertrophied guinea pig hearts induced by thyroxine. J. Chin. Pharm. Univ. 2000 31 : 451 4 (in Chinese).
33. + current in guinea pig hypertrophied ventricular myocytes induced by thyroxin. Chin. Pharmacol. Bull. 2001 17 : 174 7 (in Chinese).
34. Wang YQ, Meng Y, Dai DZ. Influence of CPU86017 and its optical isomers on blood pressure an arrhythmias induced by ischemia/reperfusion by intravenous administration in rats. J. Chin. Appl. Pharm. 2005 5 : 484 5 (in Chinese).
35. Singh BN. Beta-adrenergic blockers as antiarrhythmic and antifibrillatory compounds: An overview. J. Cardiovasc. Pharmacol. Ther. 2005 10 (Suppl. 1 S3 14.
36. Wehrens XH, Lehnart SE, Huang F et al. FKBP12.6 deficiency and defective calcium release channel (ryanodine receptor) function linked to exercise-induced sudden cardiac death. Cell 2003 113 : 829 40.
37. Jost N, Virag L, Bitay M et al. Restricting excessive cardiac action potential and QT prolongation: A vital role for IKs in human ventricular muscle. Circulation 2005 112 : 1392 9.
38. Ginghina C, Ciudin R, Lapusanu O, Kulcsar I, Selaru A, Gherasim D. Congenital short QT syndrome. A review. Rom. J. Intern. Med. 2005 43 : 165 72.
39. Kohno M, Yano M, Kobayashi S et al. A new cardioprotective agent, JTV519, improves defective channel gating of ryanodine receptor in heart failure. Am. J. Physiol. Heart Circ. Physiol. 2003 284 : H1035 42.
40. Milberg P, Reinsch N, Osada N et al. Verapamil prevents torsade de pointes by reduction of transmural dispersion of repolarization and suppression of early afterdepolarizations in an intact heart model of LQT3. Basic Res. Cardiol. 2005 100 : 365 71.