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Chemical Compound Review

Vetmedin     6-[2-(4-methoxyphenyl)-3H- benzoimidazol-5...

Synonyms: Acardi, pimobendan, pimobendane, Pimobendanum, d-Pimobendan, ...
 
 
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Disease relevance of Acardi

  • Since the modulation of myocardial necrosis and contractile dysfunction by various proinflammatory cytokines may be partially mediated by the production of nitric oxide, the effects of pimobendan on the production ofproinflammatory cytokines and NO were investigated in an animal model of viral myocarditis involving heart failure [1].
  • Calcium sensitization with pimobendan: pharmacology, haemodynamic improvement, and sudden death in patients with chronic congestive heart failure [2].
  • Although Holter analysis at 14 days, but not at 6 months, indicated increased ventricular extrasystoles in pimobendan patients, these did not lead to serious clinical events [3].
  • The finding that the mild tachycardia caused by pimobendan was not accompanied by an increase in MVO2 warrants investigation to evaluate its usefulness in the treatment of heart failure [4].
  • A double-blind, randomized, placebo-controlled study of pimobendan in dogs with dilated cardiomyopathy [5].
 

High impact information on Acardi

  • Beneficial effects of pimobendan on exercise tolerance and quality of life in patients with heart failure. Results of a multicenter trial. The Pimobendan Multicenter Research Group [6].
  • Pimobendan has almost the same mechanoenergetic effects as dobutamine but slightly greater contractile economy and coronary vasodilation [7].
  • We hypothesized that the effect of pimobendan (UD-CG 115 BS) to increase calcium sensitivity of contractile protein might result in less myocardial oxygen consumption (VO2) in comparison with dobutamine when they enhance ventricular contractility to the same extent [7].
  • Contribution of cAMP-phosphodiesterase inhibition and sensitization of the contractile proteins for calcium to the inotropic effect of pimobendan in the failing human myocardium [8].
  • The purpose of this investigation was to determine whether a positive inotropic effect of the cAMP-phosphodiesterase (PDE) inhibitor pimobendan is observed in the failing human myocardium and to study whether other factors, such as an increase in the Ca2+ sensitivity of myofilaments, play a functional role in the increase in force of contraction [8].
 

Chemical compound and disease context of Acardi

 

Biological context of Acardi

 

Anatomical context of Acardi

 

Associations of Acardi with other chemical compounds

 

Gene context of Acardi

 

Analytical, diagnostic and therapeutic context of Acardi

  • There were a total of 23 all-cause hospitalizations in the placebo group, which was significantly greater compared with 33 in the three groups treated with pimobendan (p less than 0.01) [6].
  • RESULTS: The survival of mice improved in a dose-dependent fashion such that a significant difference (p < 0.02) was found between the higher-dose pimobendan group (20 of 30 [66.7%]) and the control group (11 of 30 [36.7%]) [1].
  • The pharmacodynamic effect of pimobendan was evaluated by echocardiography [16].
  • After oral administration of 1 mg/kg to conscious dogs, compound 13 and pimobendan were still active after 6.5 h [26].
  • The most potent compounds were evaluated orally in conscious dogs with implanted Konigsberg pressure transducers to measure ventricular pressures, and their effect on left ventricular dP/dt was compared with that of 1, pimobendan, and indolidan [27].

References

  1. Pimobendan inhibits the production of proinflammatory cytokines and gene expression of inducible nitric oxide synthase in a murine model of viral myocarditis. Iwasaki, A., Matsumori, A., Yamada, T., Shioi, T., Wang, W., Ono, K., Nishio, R., Okada, M., Sasayama, S. J. Am. Coll. Cardiol. (1999) [Pubmed]
  2. Calcium sensitization with pimobendan: pharmacology, haemodynamic improvement, and sudden death in patients with chronic congestive heart failure. Hagemeijer, F. Eur. Heart J. (1993) [Pubmed]
  3. Long-term efficacy and safety of pimobendan in moderate heart failure. A double-blind parallel 6-month comparison with enalapril. The Pimobendan-Enalapril Study Group. Remme, W.J., Krayenbühl, H.P., Baumann, G., Frick, M.H., Haehl, M., Nehmiz, G., Baiker, W. Eur. Heart J. (1994) [Pubmed]
  4. Cardiovascular profile of pimobendan, a benzimidazole-pyridazinone derivative with vasodilating and inotropic properties. Verdouw, P.D., Hartog, J.M., Duncker, D.J., Roth, W., Saxena, P.R. Eur. J. Pharmacol. (1986) [Pubmed]
  5. A double-blind, randomized, placebo-controlled study of pimobendan in dogs with dilated cardiomyopathy. Fuentes, V.L., Corcoran, B., French, A., Schober, K.E., Kleemann, R., Justus, C. J. Vet. Intern. Med. (2002) [Pubmed]
  6. Beneficial effects of pimobendan on exercise tolerance and quality of life in patients with heart failure. Results of a multicenter trial. The Pimobendan Multicenter Research Group. Kubo, S.H., Gollub, S., Bourge, R., Rahko, P., Cobb, F., Jessup, M., Brozena, S., Brodsky, M., Kirlin, P., Shanes, J. Circulation (1992) [Pubmed]
  7. Mechanoenergetic effects of pimobendan in canine left ventricles. Comparison with dobutamine. Hata, K., Goto, Y., Futaki, S., Ohgoshi, Y., Yaku, H., Kawaguchi, O., Takasago, T., Saeki, A., Taylor, T.W., Nishioka, T. Circulation (1992) [Pubmed]
  8. Contribution of cAMP-phosphodiesterase inhibition and sensitization of the contractile proteins for calcium to the inotropic effect of pimobendan in the failing human myocardium. Böhm, M., Morano, I., Pieske, B., Rüegg, J.C., Wankerl, M., Zimmermann, R., Erdmann, E. Circ. Res. (1991) [Pubmed]
  9. A multicenter, randomized, double-blind, placebo-controlled trial of pimobendan, a new cardiotonic and vasodilator agent, in patients with severe congestive heart failure. Katz, S.D., Kubo, S.H., Jessup, M., Brozena, S., Troha, J.M., Wahl, J., Cohn, J.N., Sonnenblick, E.H., LeJemtel, T.H. Am. Heart J. (1992) [Pubmed]
  10. Correlations between the cardiovascular effects of pimobendan and plasma concentrations of the parent compound and of its major active metabolite, UD-CG 212 CL, in patients with congestive heart failure. Hagemeijer, F., Roth, W., Brand, H.J. J. Cardiovasc. Pharmacol. (1989) [Pubmed]
  11. Effects of the positive inotropic agents milrinone and pimobendan on the development of lethal ischemic arrhythmias in conscious dogs with recent myocardial infarction. Lynch, J.J., Uprichard, A.C., Frye, J.W., Driscoll, E.M., Kitzen, J.M., Lucchesi, B.R. J. Cardiovasc. Pharmacol. (1989) [Pubmed]
  12. Low-dose systemic phosphodiesterase III inhibitor pimobendan combined with prostacyclin therapy in a patient with severe primary pulmonary y hypertension. Watanabe, E., Shiga, T., Matsuda, N., Kajimoto, K., Naganuma, M., Kawai, A., Kasanuki, H. Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy. (2003) [Pubmed]
  13. Comparative cardiac toxicity of the i.v. administered benzimidazole pyridazinon derivative Pimobendan and its enantiomers in female Beagle dogs. Schneider, P., Güttner, J., Eckenfels, A., Heinzel, G., von Nicolai, H., Trieb, G., Lehmann, H. Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie. (1997) [Pubmed]
  14. Sensitization of dog and guinea pig heart myofilaments to Ca2+ activation and the inotropic effect of pimobendan: comparison with milrinone. Fujino, K., Sperelakis, N., Solaro, R.J. Circ. Res. (1988) [Pubmed]
  15. Comparison of hormonal and haemodynamic changes after long-term oral therapy with pimobendan or enalapril--a double-blind randomized study. Erlemeier, H.H., Kupper, W., Bleifeld, W. Eur. Heart J. (1991) [Pubmed]
  16. Pharmacokinetics and pharmacodynamics of enantiomers of pimobendan in patients with dilated cardiomyopathy and congestive heart failure after single and repeated oral dosing. Chu, K.M., Shieh, S.M., Hu, O.Y. Clin. Pharmacol. Ther. (1995) [Pubmed]
  17. The novel insulinotropic mechanism of pimobendan: direct enhancement of the exocytotic process of insulin secretory granules by increased Ca2+ sensitivity in beta-cells. Fujimoto, S., Ishida, H., Kato, S., Okamoto, Y., Tsuji, K., Mizuno, N., Ueda, S., Mukai, E., Seino, Y. Endocrinology (1998) [Pubmed]
  18. Different effects of aspirin, dipyridamole and UD-CG 115 on platelet activation in a model of vascular injury: studies with extracellular matrix covered with endothelial cells. Eldor, A., Vlodavsky, I., Fuks, Z., Muller, T.H., Eisert, W.G. Thromb. Haemost. (1986) [Pubmed]
  19. Platelet aggregation inhibitory effects of the new positive inotropic agents pimobendan and UD CG 212 in whole blood. Saniabadi, A.R., Lowe, G.D., Belch, J.J., Forbes, C.D. Cardiovasc. Res. (1989) [Pubmed]
  20. Nonsteroidal cardiotonics. 1. 2-Pyridyl-6,7-dihydro-3H,5H-pyrrolo[2,3-f]benzimidazol-6-ones, a novel class of cardiotonic agents. Mertens, A., Müller-Beckmann, B., Kampe, W., Hölck, J.P., von der Saal, W. J. Med. Chem. (1987) [Pubmed]
  21. Electrophysiological actions of the pimobendan metabolite, UD-CG 212 Cl, in guinea pig myocardium. Westfall, M.V., Wahler, G.M., Fujino, K., Solaro, R.J. J. Pharmacol. Exp. Ther. (1992) [Pubmed]
  22. Influence of levosimendan, pimobendan, and milrinone on the regional distribution of cardiac output in anaesthetized dogs. Pagel, P.S., Hettrick, D.A., Warltier, D.C. Br. J. Pharmacol. (1996) [Pubmed]
  23. The effects of reported Ca2+ sensitisers on the rates of Ca2+ release from cardiac troponin C and the troponin-tropomyosin complex. Smith, S.J., England, P.J. Br. J. Pharmacol. (1990) [Pubmed]
  24. Identification of cytochrome P-450 isoform(s) responsible for the metabolism of pimobendan in human liver microsomes. Kuriya, S., Ohmori, S., Hino, M., Ishii, I., Nakamura, H., Senda, C., Igarashi, T., Kiuchi, M., Kitada, M. Drug Metab. Dispos. (2000) [Pubmed]
  25. Differential modulation of cytokine production by drugs: implications for therapy in heart failure. Matsumori, A., Ono, K., Sato, Y., Shioi, T., Nose, Y., Sasayama, S. J. Mol. Cell. Cardiol. (1996) [Pubmed]
  26. Nonsteroidal cardiotonics. 3. New 4,5-dihydro-6-(1H-indol-5-yl)pyridazin-3(2H)-ones and related compounds with positive inotropic activities. Mertens, A., Friebe, W.G., Müller-Beckmann, B., Kampe, W., Kling, L., von der Saal, W. J. Med. Chem. (1990) [Pubmed]
  27. Nonsteroidal cardiotonics. 2. The inotropic activity of linear, tricyclic 5-6-5 fused heterocycles. von der Saal, W., Hölck, J.P., Kampe, W., Mertens, A., Müller-Beckmann, B. J. Med. Chem. (1989) [Pubmed]
 
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