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Chemical Compound Review

Siguazodan     3-cyano-2-methyl-1-[4-(4- methyl-6-oxo-4,5...

Synonyms: AG-J-51837, CHEMBL1256712, BSPBio_001354, KBioGR_000074, KBioSS_000074, ...
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Disease relevance of SkF94836

  • 9. We conclude that SK&F 94836, as an orally active inotropic/vasodilator agent with a sustained duration in vivo, has potential utility in the treatment of congestive heart failure [1].
  • The rise in IL-5 at 3 h was additionally attenuated by the PDE3 inhibitor, siguazodan, which failed to attenuate the eosinophilia at 24 h [2].

High impact information on SkF94836

  • The PDE3 inhibitor, siguazodan, was ineffective in downregulating gene expression for the proinflammatory cytokines assayed; when used in combination with the PDE4 inhibitor, the PDE3 inhibitor provided no increase in efficacy over that seen with the PDE4 inhibitor alone [3].
  • The inhibitors of PDE type 3 (SK&F 94836) and type 5 (zaprinast) failed to alter allergen-evoked eosinophil recruitment in rats [4].
  • 4. The PDE3-selective inhibitors Org 9935 (0.02 - 10 microM) and siguazodan (0.1 - 10 microM) inhibited cyclic AMP PDE activity in the pellet but not the supernatant fractions of cell homogenates, with a maximum inhibition of about 30% [5].
  • Finally, RP 73401 (IC50: 0.41 +/- 0.19 nM) inhibited anti-CD3-stimulated DNA synthesis in splenocyte preparations from M. corti-infected mice and siguazodan (10 microM) had no effect on this response, either alone or in combination with the PDE4 inhibitor [6].
  • The PDE3 inhibitor, siguazodan (10 microM), had little or no effect on IL-2 release or DNA synthesis [7].

Biological context of SkF94836


Anatomical context of SkF94836

  • 5. Detailed studies carried out on anaesthetized cats indicated that SK&F 94836 caused a balanced dilatation of both resistance and capacitance blood vessels [1].
  • However, siguazodan produced significantly greater (P<0.05), and rolipram significantly less (P<0.05), inhibition of total cAMP PDE activity in monocytes from asthmatics (n=4) than from healthy individuals (n=5). cAMP PDE activity was inhibited with equal potency by theophylline in monocytes from healthy and asthmatic subjects [10].
  • In contrast to their effects vs. allergic airway smooth muscle contraction, both milrinone and siguazodan potently relaxed leukotriene C4 (LTC4)-induced contraction in isolated trachea from non-sensitized animals [11].

Associations of SkF94836 with other chemical compounds


Gene context of SkF94836

  • Treatment of the PRP with aspirin had no effect on the potency of siguazodan [13].
  • Despite a significant increase in the biochemical activity of PDE3 in monocytes from asthmatic subjects, the PDE3 inhibitor siguazodan, failed to significantly reduce TNF alpha release from human monocytes [10].

Analytical, diagnostic and therapeutic context of SkF94836


  1. In vivo pharmacological studies with SK&F 94836, a potent inotrope/vasodilator with a sustained duration of action. Gristwood, R.W., Comer, M.B., Eden, R.J., Taylor, E.M., Turner, J.A., Wallduck, M., Owen, D.A. Br. J. Pharmacol. (1988) [Pubmed]
  2. The potential roles of cytokines, IL-5 and IL-8, and plasma cortisol in the anti-inflammatory actions of phosphodiesterase inhibitors in sensitized guinea-pig airways. Danahay, H., Broadley, K.J., McCabe, P.J., Nials, A.T., Sanjar, S. Pulmonary pharmacology & therapeutics. (1997) [Pubmed]
  3. Effects of nonselective and isozyme selective cyclic nucleotide phosphodiesterase inhibitors on antigen-induced cytokine gene expression in peripheral blood mononuclear cells. Essayan, D.M., Huang, S.K., Kagey-Sobotka, A., Lichtenstein, L.M. Am. J. Respir. Cell Mol. Biol. (1995) [Pubmed]
  4. Modulation of eotaxin formation and eosinophil migration by selective inhibitors of phosphodiesterase type 4 isoenzyme. Silva, P.M., Alves, A.C., Serra, M.F., Pires, A.L., Silva, J.P., Barreto, E.O., Cordeiro, R.S., Jose, P.J., Teixeira, M.M., Lagente, V., Martins, M.A. Br. J. Pharmacol. (2001) [Pubmed]
  5. Effect of type-selective inhibitors on cyclic nucleotide phosphodiesterase activity and insulin secretion in the clonal insulin secreting cell line BRIN-BD11. Ahmad, M., Abdel-Wahab, Y.H., Tate, R., Flatt, P.R., Pyne, N.J., Furman, B.L. Br. J. Pharmacol. (2000) [Pubmed]
  6. Suppression of anti-CD3-induced interleukin-4 and interleukin-5 release from splenocytes of Mesocestoides corti-infected BALB/c mice by phosphodiesterase 4 inhibitors. Souness, J.E., Houghton, C., Sardar, N., Withnall, M.T. Biochem. Pharmacol. (1999) [Pubmed]
  7. Evidence that cyclic AMP phosphodiesterase inhibitors suppress interleukin-2 release from murine splenocytes by interacting with a 'low-affinity' phosphodiesterase 4 conformer. Souness, J.E., Houghton, C., Sardar, N., Withnall, M.T. Br. J. Pharmacol. (1997) [Pubmed]
  8. Comparison of phosphodiesterase III, IV and dual III/IV inhibitors on bronchospasm and pulmonary eosinophil influx in guinea pigs. Underwood, D.C., Kotzer, C.J., Bochnowicz, S., Osborn, R.R., Luttmann, M.A., Hay, D.W., Torphy, T.J. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  9. Effect of isoenzyme selective phosphodiesterase inhibitors on the proliferation of murine thymus and spleen cells. Banner, K.H., Bertin, B., Moodley, I., Page, C.P. Pulmonary pharmacology. (1996) [Pubmed]
  10. A biochemical and functional assessment of monocyte phosphodiesterase activity in healthy and asthmatic subjects. Landells, L.J., Spina, D., Souness, J.E., O'Connor, B.J., Page, C.P. Pulmonary pharmacology & therapeutics. (2000) [Pubmed]
  11. Differential inhibition by selective phosphodiesterase inhibitors of antigen, LTC4 and histamine-induced contraction of guinea-pig isolated trachea. Planquois, J.M., Ruffin-Morin, Y., Lagente, V., Payne, A.N., Dahl, S.G. Pulmonary pharmacology. (1996) [Pubmed]
  12. Comparison of the effects of selective inhibitors of phosphodiesterase types III and IV in airway smooth muscle with differing beta-adrenoceptor subtypes. Tomkinson, A., Karlsson, J.A., Raeburn, D. Br. J. Pharmacol. (1993) [Pubmed]
  13. The effects of siguazodan, a selective phosphodiesterase inhibitor, on human platelet function. Murray, K.J., England, P.J., Hallam, T.J., Maguire, J., Moores, K., Reeves, M.L., Simpson, A.W., Rink, T.J. Br. J. Pharmacol. (1990) [Pubmed]
  14. Effects of phosphodiesterase inhibitors on interleukin-4 and interleukin-13 generation from human basophils. Eskandari, N., Wickramasinghe, T., Peachell, P.T. Br. J. Pharmacol. (2004) [Pubmed]
  15. Phosphodiesterase activity in neutrophils from horses with chronic obstructive pulmonary disease. Rickards, K.J., Page, C.P., Lees, P., Cunningham, F.M. Vet. Immunol. Immunopathol. (2000) [Pubmed]
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