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Chemical Compound Review

zaprinast     3-(2-propoxyphenyl)- 2,4,7,8,9...

Synonyms: Zaprinastum, Prestwick_655, Lopac-Z-0878, Tocris-0947, CHEMBL28079, ...
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Disease relevance of zaprinast


Psychiatry related information on zaprinast


High impact information on zaprinast

  • The relaxation caused by either electrical stimulation or nitric oxide was enhanced by a selective inhibitor of cyclic guanosine monophosphate (GMP) phosphodiesterase (M&B 22,948) [8].
  • This difference was not related to differences in binding of 125I-ANP to IMCD cells, but was abolished when cGMP accumulation was measured in the presence of 10(-3) M isobutylmethylxanthine or zaprinast (M&B 22,948), two different inhibitors of cyclic nucleotide phosphodiesterases (PDEs) [9].
  • Infusion of zaprinast (10 micrograms/min) into one renal artery of nephrotic rats normalized both the natriuretic response to volume expansion and the increase in UcGMPV from the infused, but not the contralateral, kidney [9].
  • Neither 1H-(1,2,4)oxadiazolo[4,3-alpha]quinoxalin-1-one nor zaprinast influenced the cytostatic effect of NO or DFMO or their ability to activate these signal transduction pathways [10].
  • PDE11A is sensitive to the nonselective PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX) as well as zaprinast and dipyridamole, inhibitors that are generally considered relatively specific for the cGMP-selective PDEs, with IC(50) values of 49.8 microM, 12.0 microM, and 0.37 microM, respectively [11].

Chemical compound and disease context of zaprinast


Biological context of zaprinast

  • After 24 hours of culture, the various PDE inhibitors differed in their ability to induce apoptosis, with zaprinast displaying no killing effect [15].
  • Moreover, the effects of the intravenous administration of Zaprinast (15 microgram/kg/min and 30 microgram/kg/min) on renal plasma flow (RPF), glomerular filtration rate (GFR), and urinary sodium excretion (U(Na)V) were evaluated in 10 conscious control rats and 10 conscious cirrhotic rats with ascites [1].
  • We report that zaprinast and IBMX increased the amplitudes and retarded the kinetics of physiological light responses [16].
  • Wild-type and mutant proteins were compared with respect to Km for cGMP, kcat, and IC50 for zaprinast [17].
  • Manipulation of the glutathione homeostasis (buthionine-(S,R)-sulfoximine) and the cGMP pathway (1H-(1,2,4)oxadiazolo[4,3-alpha]quinoxaline-1-one; zaprinast) did not interfere with the protective effect of LPS [18].

Anatomical context of zaprinast


Associations of zaprinast with other chemical compounds

  • The increase in cavernosal pressure in response to cavernosal nerve stimulation was enhanced in animals transfected with eNOS, and erectile responses to acetylcholine and zaprinast were enhanced at a time when the erectile response to the NO donor sodium 1-(N,N-diethylamino)diazen-1-ium-1,2-diolate was not altered [24].
  • PDE9A is insensitive (up to 100 microM) to a variety of PDE inhibitors including rolipram, vinpocetine, SKF-94120, dipyridamole, and 3-isobutyl-1-methyl-xanthine but is inhibited (IC50 = 35 microM) by zaprinast, a PDE5 inhibitor [25].
  • In contrast, mediator release from basophils was not inhibited by either siguazodan or SK&F 95654, inhibitors of the cGMP-inhibited PDE (PDE III) or zaprinast, an inhibitor of the cGMP-specific PDE (PDE V) [21].
  • SK&F 95654 failed to elevate basophil cAMP in these experiments whereas zaprinast induced significant increases in cAMP content [21].
  • The present study was designed to determine the role of potassium channels in the relaxations to NO donors 3-morpholinosydnonimine (SIN-1) and sodium nitroprusside (SNP), as well as 8-bromo-3',5' -cGMP (a synthetic analogue of cGMP) and zaprinast (a selective cGMP phosphodiesterase inhibitor) [26].

Gene context of zaprinast

  • The stimulatory effect of VEGF was potentiated by the selective cGMP phosphodiesterase inhibitor zaprinast (0.1 mmol/l) [27].
  • Zaprinast (10-5 M) a phosphodiesterase type V (PDE V) inhibitor, had no effect on the response to SPER-NO in vessels from eNOS WT or KO mice [28].
  • ANP as well as Zaprinast, a selective inhibitor of cGMP phosophodiesterase, inhibited renal Na+, K+-ATPase activity in wild type mice but had no such effect in mice lacking DARPP-32 [29].
  • 3. ANP (10(-11) to 10(-6) M), a NPR-C ligand, C-ANF4-23 (10(-11) to 10(-6) M) and zaprinast alone had no significant effect on either basal or serum-stimulated DNA synthesis or fibroblast number [30].
  • Zaprinast, a cGMP-specific phosphodiesterase inhibitor, could enhance the inhibitory effect of ANP on oocyte maturation [31].

Analytical, diagnostic and therapeutic context of zaprinast


  1. Increased activity of guanosine 3'-5'-cyclic monophosphate phosphodiesterase in the renal tissue of cirrhotic rats with ascites. Angeli, P., Jiménez, W., Veggian, R., Fasolato, S., Volpin, R., MacHenzie, H.S., Craighero, R., Libera, V.D., Sticca, A., Arroyo, V., Gatta, A. Hepatology (2000) [Pubmed]
  2. The cGMP phosphodiesterase inhibitor zaprinast enhances the effect of nitric oxide. Thusu, K.G., Morin, F.C., Russell, J.A., Steinhorn, R.H. Am. J. Respir. Crit. Care Med. (1995) [Pubmed]
  3. Zaprinast accelerates recovery from established acute renal failure in the rat. Guan, Z., Miller, S.B., Greenwald, J.E. Kidney Int. (1995) [Pubmed]
  4. Cyclic-3',5'-nucleotide phosphodiesterase isozymes in cell biology and pathophysiology of the kidney. Dousa, T.P. Kidney Int. (1999) [Pubmed]
  5. Restoration of learning ability in hyperammonemic rats by increasing extracellular cGMP in brain. Erceg, S., Monfort, P., Hernandez-Viadel, M., Llansola, M., Montoliu, C., Felipo, V. Brain Res. (2005) [Pubmed]
  6. Possible role of nitric oxide-cyclic GMP pathway in object recognition memory: effects of 7-nitroindazole and zaprinast. Prickaerts, J., Steinbusch, H.W., Smits, J.F., de Vente, J. Eur. J. Pharmacol. (1997) [Pubmed]
  7. Phosphodiesterase 5 inhibitors and nitrergic transmission-from zaprinast to sildenafil. Gibson, A. Eur. J. Pharmacol. (2001) [Pubmed]
  8. Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. Rajfer, J., Aronson, W.J., Bush, P.A., Dorey, F.J., Ignarro, L.J. N. Engl. J. Med. (1992) [Pubmed]
  9. Cellular basis for blunted volume expansion natriuresis in experimental nephrotic syndrome. Valentin, J.P., Qiu, C., Muldowney, W.P., Ying, W.Z., Gardner, D.G., Humphreys, M.H. J. Clin. Invest. (1992) [Pubmed]
  10. Role of p42/p44 mitogen-activated-protein kinase and p21waf1/cip1 in the regulation of vascular smooth muscle cell proliferation by nitric oxide. Bauer, P.M., Buga, G.M., Ignarro, L.J. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  11. Molecular cloning and characterization of a distinct human phosphodiesterase gene family: PDE11A. Fawcett, L., Baxendale, R., Stacey, P., McGrouther, C., Harrow, I., Soderling, S., Hetman, J., Beavo, J.A., Phillips, S.C. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  12. Effects of zaprinast and rolipram on platelet aggregation and arrhythmias following myocardial ischaemia and reperfusion in anaesthetized rabbits. Holbrook, M., Coker, S.J. Br. J. Pharmacol. (1991) [Pubmed]
  13. N omega-nitro-L-arginine attenuates the accumulation of aortic cyclic GMP and the hypotension produced by zaprinast. Dundore, R.L., Pratt, P.F., O'Connor, B., Buchholz, R.A., Pagani, E.D. Eur. J. Pharmacol. (1991) [Pubmed]
  14. Prolonged pulmonary vasodilator action of inhaled nitric oxide by Zaprinast in awake lambs. Ichinose, F., Adrie, C., Hurford, W.E., Zapol, W.M. J. Appl. Physiol. (1995) [Pubmed]
  15. Sildenafil and vardenafil, types 5 and 6 phosphodiesterase inhibitors, induce caspase-dependent apoptosis of B-chronic lymphocytic leukemia cells. Sarfati, M., Mateo, V., Baudet, S., Rubio, M., Fernandez, C., Davi, F., Binet, J.L., Delic, J., Merle-Beral, H. Blood (2003) [Pubmed]
  16. Inhibitors of cyclic-GMP phosphodiesterase alter excitation of Limulus ventral photoreceptors in Ca(2+)-dependent fashion. Johnson, E.C., O'Day, P.M. J. Neurosci. (1995) [Pubmed]
  17. Potential roles of conserved amino acids in the catalytic domain of the cGMP-binding cGMP-specific phosphodiesterase. Turko, I.V., Francis, S.H., Corbin, J.D. J. Biol. Chem. (1998) [Pubmed]
  18. Apical, but not basolateral, endotoxin preincubation protects alveolar epithelial cells against hydrogen peroxide-induced loss of barrier function: the role of nitric oxide synthesis. Rose, F., Guthmann, B., Tenenbaum, T., Fink, L., Ghofrani, A., Weissmann, N., König, P., Ermert, L., Dahlem, G., Haenze, J., Kummer, W., Seeger, W., Grimminger, F. J. Immunol. (2002) [Pubmed]
  19. Endothelium-dependent modulation of cGMP levels and intrinsic smooth muscle tone in isolated bovine intrapulmonary artery and vein. Ignarro, L.J., Byrns, R.E., Wood, K.S. Circ. Res. (1987) [Pubmed]
  20. Effect of sodium-potassium pump inhibitors and membrane-depolarizing agents on sodium nitroprusside-induced relaxation and cyclic guanosine monophosphate accumulation in rat aorta. Rapoport, R.M., Schwartz, K., Murad, F. Circ. Res. (1985) [Pubmed]
  21. Preliminary identification and role of phosphodiesterase isozymes in human basophils. Peachell, P.T., Undem, B.J., Schleimer, R.P., MacGlashan, D.W., Lichtenstein, L.M., Cieslinski, L.B., Torphy, T.J. J. Immunol. (1992) [Pubmed]
  22. Novel alternative splice variants of cGMP-binding cGMP-specific phosphodiesterase. Kotera, J., Fujishige, K., Akatsuka, H., Imai, Y., Yanaka, N., Omori, K. J. Biol. Chem. (1998) [Pubmed]
  23. Inhibition and stimulation of photoreceptor phosphodiesterases by dipyridamole and M&B 22,948. Gillespie, P.G., Beavo, J.A. Mol. Pharmacol. (1989) [Pubmed]
  24. Gene transfer of endothelial nitric oxide synthase to the penis augments erectile responses in the aged rat. Champion, H.C., Bivalacqua, T.J., Hyman, A.L., Ignarro, L.J., Hellstrom, W.J., Kadowitz, P.J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  25. Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase. Fisher, D.A., Smith, J.F., Pillar, J.S., St Denis, S.H., Cheng, J.B. J. Biol. Chem. (1998) [Pubmed]
  26. Role of potassium channels in relaxations of canine middle cerebral arteries induced by nitric oxide donors. Onoue, H., Katusic, Z.S. Stroke (1997) [Pubmed]
  27. Upregulation of angiotensin-converting enzyme by vascular endothelial growth factor. Saijonmaa, O., Nyman, T., Kosonen, R., Fyhrquist, F. Am. J. Physiol. Heart Circ. Physiol. (2001) [Pubmed]
  28. Autoregulation of nitric oxide-soluble guanylate cyclase-cyclic GMP signalling in mouse thoracic aorta. Hussain, M.B., Hobbs, A.J., MacAllister, R.J. Br. J. Pharmacol. (1999) [Pubmed]
  29. Increased blood pressure and loss of anp-induced natriuresis in mice lacking DARPP-32 gene. Eklöf, A.C., Holtbäck, U., Svennilson, J., Fienberg, A., Greengard, P., Aperia, A. Clin. Exp. Hypertens. (2001) [Pubmed]
  30. Effect of atrial natriuretic peptide and cyclic GMP phosphodiesterase inhibition on collagen synthesis by adult cardiac fibroblasts. Redondo, J., Bishop, J.E., Wilkins, M.R. Br. J. Pharmacol. (1998) [Pubmed]
  31. Atrial natriuretic peptide inhibits the actions of FSH and forskolin in meiotic maturation of pig oocytes via different signalling pathways. Zhang, M., Tao, Y., Zhou, B., Xie, H., Wang, F., Lei, L., Huo, L., Sun, Q., Xia, G. J. Mol. Endocrinol. (2005) [Pubmed]
  32. cGMP and atrial natriuretic factor regulate cell volume of rabbit atrial myocytes. Clemo, H.F., Baumgarten, C.M. Circ. Res. (1995) [Pubmed]
  33. Evidence for involvement of the cGMP-protein kinase G signaling system in the induction of long-term depression, but not long-term potentiation, in the dentate gyrus in vitro. Wu, J., Wang, Y., Rowan, M.J., Anwyl, R. J. Neurosci. (1998) [Pubmed]
  34. Effects of intravenous Zaprinast and inhaled nitric oxide on pulmonary hemodynamics and gas exchange in an ovine model of acute respiratory distress syndrome. Adrie, C., Holzmann, A., Hirani, W.M., Zapol, W.M., Hurford, W.E. Anesthesiology (2000) [Pubmed]
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