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Chemical Compound Review

Piroximona     4-ethyl-5-pyridin-4- ylcarbonyl-1,3...

Synonyms: Piroximone, Piroximonum, CHEMBL58355, SureCN119758, MDL-19205, ...
 
 
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Disease relevance of PIROXIMONE HYDROCHLORIDE

 

High impact information on PIROXIMONE HYDROCHLORIDE

  • Persistent hemodynamic effects without long-term clinical benefits in response to oral piroximone (MDL 19,205) in patients with congestive heart failure [1].
  • Three phosphodiesterase (PDE) type III inhibitors were tested and found to inhibit Xenopus oocyte maturation induced by insulin with apparent IC50 values of 2.2 +/- 0.2 microM Cl-930, 25 +/- 3 microM imazodan (Cl-914), and 786 +/- 237 microM piroximone (MDL 19,205) [6].
  • The same rank order of potencies was observed for inhibition of insulin-like growth factor-I (IGF-I)-induced oocyte maturation, with IC50 values of 5.5 +/- 0.9 microM Cl-930, 54 +/- 4 microM imazodan, and 1190 +/- 395 microM piroximone [6].
  • In four other patients, a single intravenous dose of piroximone (1 mg/kg) resulted in a 35% increase in the first derivative of left ventricular pressure (dP/dt) from 796 to 1,068 mm Hg/s (p less than 0.01) [7].
  • Additionally, a further decrease in pulmonary capillary wedge pressure by 13 and 11% (P < 0.05) and in pulmonary vascular resistance by 21 and 19% (P < 0.05) was observed at the piroximone-infusion rates of 5 and 10 micrograms.kg-1.min-1, respectively [8].
 

Chemical compound and disease context of PIROXIMONE HYDROCHLORIDE

 

Biological context of PIROXIMONE HYDROCHLORIDE

 

Anatomical context of PIROXIMONE HYDROCHLORIDE

 

Associations of PIROXIMONE HYDROCHLORIDE with other chemical compounds

 

Gene context of PIROXIMONE HYDROCHLORIDE

 

Analytical, diagnostic and therapeutic context of PIROXIMONE HYDROCHLORIDE

  • The increase in stroke work index with a concomitant decrease in left ventricular filling pressure indicates an improvement in systolic performance after treatment with piroximone [24].
  • In a subgroup of 10 patients who underwent equilibrium gated radionuclide blood pool scintigraphy before and after intravenous piroximone, end-diastolic volume index tended to increase (106 +/- 42 to 132 +/- 60 ml/m2; p = 0.07), whereas left ventricular filling pressure decreased significantly (26 +/- 8 to 19 +/- 9 mm Hg; p less than 0.01) [24].
  • Determination of piroximone in human plasma by high-performance liquid chromatography [25].
  • A rapid and selective high-performance liquid chromatographic (HPLC) method using solid-phase extraction (SPE) for measuring piroximone in plasma samples has been developed [25].
  • Controlled clinical trials should be undertaken to determine the ultimate efficacy and safety of piroximone in these patients [12].

References

  1. Persistent hemodynamic effects without long-term clinical benefits in response to oral piroximone (MDL 19,205) in patients with congestive heart failure. Petein, M., Levine, T.B., Cohn, J.N. Circulation (1986) [Pubmed]
  2. Assessment of the biotransformation of the cardiotonic agent piroximone by high-performance liquid chromatography and gas chromatography-mass spectrometry. Berg-Candolfi, M., Borlakoglu, J.T., Dulery, B., Jehl, F., Haegele, K.D. J. Chromatogr. (1992) [Pubmed]
  3. Pharmacokinetics of piroximone after oral and intravenous administration to patients with renal insufficiency. Fauvel, J.P., Bernard, N., Laville, M., Pozet, N., Sassard, J., Zech, P.Y. British journal of clinical pharmacology. (1995) [Pubmed]
  4. Comparison of the haemodynamic effects of enoximone and piroximone in patients after cardiac surgery. Patel, A., Caldicott, L.D., Skoyles, J.R., Das, P., Sherry, K.M. British journal of anaesthesia. (1993) [Pubmed]
  5. Effects of long-term therapy with oral piroximone on resting hemodynamics, peak aerobic capacity, and the anaerobic threshold in patients with heart failure. Nemanich, J.W., Shurman, A.J., Rossen, J.D., Kremser, C., Davis, F., Rajfer, S.I. J. Cardiovasc. Pharmacol. (1987) [Pubmed]
  6. Type III phosphodiesterase plays a necessary role in the growth-promoting actions of insulin, insulin-like growth factor-I, and Ha p21ras in Xenopus laevis oocytes. Sadler, S.E. Mol. Endocrinol. (1991) [Pubmed]
  7. Hemodynamic effects of a new inotropic agent, piroximone (MDL 19205), in patients with chronic heart failure. Petein, M., Levine, T.B., Cohn, J.N. J. Am. Coll. Cardiol. (1984) [Pubmed]
  8. Additive haemodynamic effects of piroximone and prostacyclin in severe chronic heart failure. Albo, C., Saal, J.P., Lellouche, D., Habbal, R., Benvenuti, C., Deleuze, P., Loisance, D., Castaigne, A., Dubois-Randé, J.L. Eur. Heart J. (1994) [Pubmed]
  9. Hemodynamic and regional blood flow response to piroximone (MDL 19,205) in dogs with congestive heart failure: a comparison with dobutamine. Petein, M., Heppner, B., Bache, R.J., Cohn, J.N., Pierpont, G.L. J. Pharmacol. Exp. Ther. (1987) [Pubmed]
  10. Acute hemodynamic effects of piroximone (MDL 19,205) in patients with moderate congestive heart failure: comparison with sodium nitroprusside. Arbogast, R., Brandt, C.M., Fincker, J.L., Schechter, P.J. J. Cardiovasc. Pharmacol. (1986) [Pubmed]
  11. Myocardial energetics: experimental and clinical studies to address its determinants and aerobic limit. Weber, K.T., Janicki, J.S., Sundram, P. Basic Res. Cardiol. (1989) [Pubmed]
  12. Piroximone (MDL 19,205) in the treatment of unstable and stable chronic cardiac failure. Weber, K.T., Janicki, J.S., Jain, M.C. Am. Heart J. (1987) [Pubmed]
  13. Phosphodiesterase-inhibitors enoximone and piroximone in cardiac surgery: influence on platelet count and function. Boldt, J., Knothe, C., Zickmann, B., Herold, C., Dapper, E., Hempelmann, G. Intensive care medicine. (1992) [Pubmed]
  14. Effects of piroximone on the right ventricular function in severe heart failure patients. Saal, J.P., Habbal, R., Estagnasie, P., Lellouche, D., Castaigne, A., Dubois-Randé, J.L. Intensive care medicine. (1994) [Pubmed]
  15. Circulatory effects of the PDE-inhibitors piroximone and enoximone. Boldt, J., Knothe, C., Zickmann, B., Schindler, E., Stertmann, W.A., Hempelmann, G. British journal of clinical pharmacology. (1993) [Pubmed]
  16. Piroximone, dobutamine and nitroprusside: comparative effects on haemodynamics in patients with congestive heart failure. Baumann, G., Ningel, K., Vieweg, J., Joder-Ohlenbusch, A.M., Cremer, G. Eur. Heart J. (1991) [Pubmed]
  17. Cyclic GMP modulates release of norepinephrine from adrenergic nerves innervating canine arteries. Greenberg, S.S., Cantor, E., Diecke, F.P., Peevy, K., Tanaka, T.P. Am. J. Hypertens. (1991) [Pubmed]
  18. Studies on the mechanism of the positive inotropic effect of piroximone in cat papillary muscle. Cheng, H.C., Kariya, T., Gleason, E.M., Dage, R.C. J. Cardiovasc. Pharmacol. (1985) [Pubmed]
  19. Metabolism and pharmacokinetics of the cardiotonic agent piroximone and of its major metabolite in dog. Berg-Candolfi, M., Dulery, B., Jehl, F., Haegele, K.D. Xenobiotica (1995) [Pubmed]
  20. Phosphodiesterase inhibitors: alterations in systemic and coronary hemodynamics. Chatterjee, K. Basic Res. Cardiol. (1989) [Pubmed]
  21. Long-term oral therapy of congestive heart failure with phosphodiesterase inhibitors. Wood, M.A., Hess, M.L. Am. J. Med. Sci. (1989) [Pubmed]
  22. Inotropic responses to cyclic nucleotide phosphodiesterase inhibitors in immature and adult rabbit myocardium. Artman, M., Kithas, P.A., Wike, J.S., Crump, D.B., Strada, S.J. J. Cardiovasc. Pharmacol. (1989) [Pubmed]
  23. Effects of a standardized meal on the pharmacokinetics of the new cardiotonic agent piroximone. Haegele, K.D., Hinze, C., Joder-Ohlenbusch, A.M., Cremer, G., Borlak, J. Arzneimittel-Forschung. (1991) [Pubmed]
  24. Hemodynamic and clinical evaluation of piroximone, a new inotrope-vasodilator agent, in severe congestive heart failure. Axelrod, R.J., De Marco, T., Dae, M., Botvinick, E.H., Chatterjee, K. J. Am. Coll. Cardiol. (1987) [Pubmed]
  25. Determination of piroximone in human plasma by high-performance liquid chromatography. Ha, H.R., Follath, F. Therapeutic drug monitoring. (1994) [Pubmed]
 
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