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. 1991 Jun;103(2):1556–1560. doi: 10.1111/j.1476-5381.1991.tb09826.x

Effects of midaglizole, a new hypoglycaemic drug on the electrophysiological properties of guinea-pig papillary muscle.

N Noguchi 1, J Hasegawa 1, H Mashiba 1
PMCID: PMC1908340  PMID: 1884109

Abstract

1. The electrophysiological effects of midaglizole, a new oral hypoglycaemic agent which is an alpha 2-adrenoceptor antagonist, were assessed in the reserpinized ventricular myocardium of the guinea-pig. 2. Midaglizole suppressed the maximal rate of rise (Vmax) and the amplitude of action potentials (APA) of the fast and the slow responses in a concentration-dependent manner without influencing the resting potentials. 3. Voltage-dependency of the Vmax block of the action potentials by midaglizole (10 microM) did not appear in solutions containing various concentrations of KCl. 4. It is concluded that midaglizole has inhibitory effects on the fast Na+ and slow Ca2+ currents of the membrane independent of the blockade of myocardial alpha-adrenoceptors, and that these effects may be significant in some clinical uses of the drug.

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Selected References

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  1. Azuma J., Vogel S., Josephson I., Sperelakis N. Yohimbine blockade of ionic channels in myocardial cells. Eur J Pharmacol. 1978 Sep 15;51(2):109–119. doi: 10.1016/0014-2999(78)90335-7. [DOI] [PubMed] [Google Scholar]
  2. Briggs G. M., Meier C. F., Jr Effect of yohimbine on action potentials recorded from isolated canine ventricular myocytes. Eur J Pharmacol. 1986 Aug 7;127(1-2):125–128. doi: 10.1016/0014-2999(86)90213-x. [DOI] [PubMed] [Google Scholar]
  3. Dukes I. D., Vaughan Williams E. M. Electrophysiological effects of alpha-adrenoceptor antagonists in rabbit sino-atrial node, cardiac Purkinje cells and papillary muscles. Br J Pharmacol. 1984 Oct;83(2):419–426. doi: 10.1111/j.1476-5381.1984.tb16502.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ehara T., Inazawa M. Calcium-dependent slow action potentials in potassium-depolarized guinea-pig ventricular myocardium enhanced by barium ions. Naunyn Schmiedebergs Arch Pharmacol. 1980;315(1):47–54. doi: 10.1007/BF00504229. [DOI] [PubMed] [Google Scholar]
  5. Gintant G. A., Hoffman B. F., Naylor R. E. The influence of molecular form of local anesthetic-type antiarrhythmic agents on reduction of the maximum upstroke velocity of canine cardiac Purkinje fibers. Circ Res. 1983 Jun;52(6):735–746. doi: 10.1161/01.res.52.6.735. [DOI] [PubMed] [Google Scholar]
  6. Gülch R. W., Mohrmann J., Schultheiss S. Influence of the alpha-adrenoceptor antagonist urapidil on transmembrane action potentials of mammalian myocardium. Arzneimittelforschung. 1986 Oct;36(10):1477–1480. [PubMed] [Google Scholar]
  7. Hammermeister K. E., Boerth R. C., Warbasse J. R. The comparative inotropic effects of six clinically used antiarrhythmic agents. Am Heart J. 1972 Nov;84(5):643–652. doi: 10.1016/0002-8703(72)90179-2. [DOI] [PubMed] [Google Scholar]
  8. Hasegawa J., Hirai S., Saitoh M., Kotake H., Mashiba H. Antiarrhythmic effects of alpha-adrenoceptor antagonists in guinea pig ventricular myocardium. J Am Coll Cardiol. 1988 Dec;12(6):1590–1598. doi: 10.1016/s0735-1097(88)80030-5. [DOI] [PubMed] [Google Scholar]
  9. Hisatome I., Kiyosue T., Imanishi S., Arita M. Isoproterenol inhibits residual fast channel via stimulation of beta-adrenoceptors in guinea-pig ventricular muscle. J Mol Cell Cardiol. 1985 Jul;17(7):657–665. doi: 10.1016/s0022-2828(85)80065-1. [DOI] [PubMed] [Google Scholar]
  10. Hoffmeister H. M., Hepp A., Seipel L. Negative inotropic effect of class-I-antiarrhythmic drugs: comparison of flecainide with disopyramide and quinidine. Eur Heart J. 1987 Oct;8(10):1126–1132. doi: 10.1093/oxfordjournals.eurheartj.a062178. [DOI] [PubMed] [Google Scholar]
  11. Inazawa M., Ehara T., Hasegawa J. Effects of low-sodium solutions on the calcium-dependent slow action potentials in potassium-depolarized guinea-pig ventricular muscle. Jpn J Physiol. 1982;32(2):315–319. doi: 10.2170/jjphysiol.32.315. [DOI] [PubMed] [Google Scholar]
  12. Kameda K. Y., Koyama I., Abiko Y. Comparative study on the effects of a hypoglycemic 2-substituted-2-imidazoline derivative (DG-5128) and tolbutamide on insulin secretion from and insulin synthesis in the isolated rat pancreatic islets. Biochim Biophys Acta. 1981 Oct 12;677(2):263–268. doi: 10.1016/0304-4165(81)90094-5. [DOI] [PubMed] [Google Scholar]
  13. Kameda K., Ono S., Abiko Y. Hypoglycemic action of 2-[2-(4,5-dihydro-1H-imidazol-2-yl)-1-phenylethyl]pyridine dihydrochloride sesquihydrate (DG-5128), a new hypoglycemic agent. Arzneimittelforschung. 1982;32(1):39–44. [PubMed] [Google Scholar]
  14. Kameda K., Ono S., Koyama I., Abiko Y. Insulin releasing action of 2-[2-(4,5-dihydro-1H-imadazol-2-yl)-1-phenylethyl] pyridine dihydrochloride sesquihydrate (DG-5128), a new, orally effective hypoglycaemic agent. Acta Endocrinol (Copenh) 1982 Mar;99(3):410–415. doi: 10.1530/acta.0.0990410. [DOI] [PubMed] [Google Scholar]
  15. Kashiwagi A., Harano Y., Suzuki M., Kojima H., Harada M., Nishio Y., Shigeta Y. New alpha 2-adrenergic blocker (DG-5128) improves insulin secretion and in vivo glucose disposal in NIDDM patients. Diabetes. 1986 Oct;35(10):1085–1089. doi: 10.2337/diab.35.10.1085. [DOI] [PubMed] [Google Scholar]
  16. Kawazu S., Suzuki M., Negishi K., Ishii J., Sando H., Katagiri H., Kanazawa Y., Yamanouchi S., Akanuma Y., Kajinuma H. Initial phase II clinical studies on midaglizole (DG-5128). A new hypoglycemic agent. Diabetes. 1987 Feb;36(2):221–226. doi: 10.2337/diab.36.2.221. [DOI] [PubMed] [Google Scholar]
  17. Kawazu S., Suzuki M., Negishi K., Watanabe T., Ishii J. Studies of midaglizole (DG-5128). A new type of oral hypoglycemic drug in healthy subjects. Diabetes. 1987 Feb;36(2):216–220. doi: 10.2337/diab.36.2.216. [DOI] [PubMed] [Google Scholar]
  18. Kimura S., Cameron J. S., Kozlovskis P. L., Bassett A. L., Myerburg R. J. Delayed afterdepolarizations and triggered activity induced in feline Purkinje fibers by alpha-adrenergic stimulation in the presence of elevated calcium levels. Circulation. 1984 Dec;70(6):1074–1082. doi: 10.1161/01.cir.70.6.1074. [DOI] [PubMed] [Google Scholar]
  19. Kiyosue T., Arita M. Magnesium restores high K-induced inactivation of the fast Na channel in guinea pig ventricular muscle. Pflugers Arch. 1982 Oct;395(1):78–80. doi: 10.1007/BF00584973. [DOI] [PubMed] [Google Scholar]
  20. Kohlhardt M., Seifert C. Inhibition of Vmax of the action potential by propafenone and its voltage-, time- and pH-dependence in mammalian ventricular myocardium. Naunyn Schmiedebergs Arch Pharmacol. 1980;315(1):55–62. doi: 10.1007/BF00504230. [DOI] [PubMed] [Google Scholar]
  21. Kotake H., Hirai S., Watanabe M., Miyamoto J., Takami T., Hasegawa J., Mashiba H. Effect of the alpha-adrenoceptor antagonist urapidil on the pacemaker activity of rabbit sino-atrial node preparations. Arch Int Pharmacodyn Ther. 1988 Jul-Aug;294:149–158. [PubMed] [Google Scholar]
  22. Lasseter K. C., Levey G. S., Palmer R. F., McCarthy J. S. The effect of sulfonylurea drugs on rabbit myocardial contractility, canine purkinje fiber automaticity, and adenyl cyclase activity from rabbit and human hearts. J Clin Invest. 1972 Sep;51(9):2429–2434. doi: 10.1172/JCI107056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lechat P., Schmitt H. Interactions between the autonomic nervous system and the cardiovascular effects of ouabain in guinea-pigs. Eur J Pharmacol. 1982 Feb 19;78(1):21–32. doi: 10.1016/0014-2999(82)90368-5. [DOI] [PubMed] [Google Scholar]
  24. Levine J. H., Morganroth J., Kadish A. H. Mechanisms and risk factors for proarrhythmia with type Ia compared with Ic antiarrhythmic drug therapy. Circulation. 1989 Oct;80(4):1063–1069. doi: 10.1161/01.cir.80.4.1063. [DOI] [PubMed] [Google Scholar]
  25. Mugelli A., Amerini S., Piazzesi G., Cerbai E., Giotti A. Enhancement by norepinephrine of automaticity in sheep cardiac Purkinje fibers exposed to hypoxic glucose-free Tyrode's solution: a role for alpha-adrenoceptors? Circulation. 1986 Jan;73(1):180–188. doi: 10.1161/01.cir.73.1.180. [DOI] [PubMed] [Google Scholar]
  26. Northover B. J. A comparison of the electrophysiological actions of phentolamine with those of some other antiarrhythmic drugs on tissues isolated from the rat heart. Br J Pharmacol. 1983 Sep;80(1):85–93. doi: 10.1111/j.1476-5381.1983.tb11053.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rosen M. R., Weiss R. M., Danilo P., Jr Effect of alpha adrenergic agonists and blockers on Purkinje fiber transmembrane potentials and automaticity in the dog. J Pharmacol Exp Ther. 1984 Dec;231(3):566–571. [PubMed] [Google Scholar]
  28. Sheridan D. J., Penkoske P. A., Sobel B. E., Corr P. B. Alpha adrenergic contributions to dysrhythmia during myocardial ischemia and reperfusion in cats. J Clin Invest. 1980 Jan;65(1):161–171. doi: 10.1172/JCI109647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sheu S. S., Lederer W. J. Lidocaine's negative inotropic and antiarrhythmic actions. Dependence on shortening of action potential duration and reduction of intracellular sodium activity. Circ Res. 1985 Oct;57(4):578–590. doi: 10.1161/01.res.57.4.578. [DOI] [PubMed] [Google Scholar]
  30. Stanton M. S., Prystowsky E. N., Fineberg N. S., Miles W. M., Zipes D. P., Heger J. J. Arrhythmogenic effects of antiarrhythmic drugs: a study of 506 patients treated for ventricular tachycardia or fibrillation. J Am Coll Cardiol. 1989 Jul;14(1):209–217. doi: 10.1016/0735-1097(89)90074-0. [DOI] [PubMed] [Google Scholar]
  31. Thandroyen F. T., Worthington M. G., Higginson L. M., Opie L. H. The effect of alpha- and beta-adrenoceptor antagonist agents on reperfusion ventricular fibrillation and metabolic status in the isolated perfused rat heart. J Am Coll Cardiol. 1983 Apr;1(4):1056–1066. doi: 10.1016/s0735-1097(83)80108-9. [DOI] [PubMed] [Google Scholar]
  32. Thomas G. P., Tripathi R. M. Effects of alpha-adrenoceptor agonists and antagonists on ouabain-induced arrhythmias and cardiac arrest in guinea-pig. Br J Pharmacol. 1986 Oct;89(2):385–388. doi: 10.1111/j.1476-5381.1986.tb10271.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Windisch H., Tritthart H. A. Calcium ion effects on the rising phases of action potentials obtained from guinea-pig papillary muscles at different potassium concentrations. J Mol Cell Cardiol. 1981 May;13(5):457–469. doi: 10.1016/0022-2828(81)90263-7. [DOI] [PubMed] [Google Scholar]
  34. Yamanaka K., Kigoshi S., Muramatsu I. Selective interaction of DG-5128 with a low agonist affinity state of alpha-2 adrenoceptor. Jpn J Pharmacol. 1985 Mar;37(3):293–295. doi: 10.1254/jjp.37.293. [DOI] [PubMed] [Google Scholar]
  35. Yamanaka K., Kigoshi S., Muramatsu I. The selectivity of DG-5128 as an alpha 2-adrenoceptor antagonist. Eur J Pharmacol. 1984 Nov 27;106(3):625–628. doi: 10.1016/0014-2999(84)90068-2. [DOI] [PubMed] [Google Scholar]

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