Molecular mechanisms of the effects of sildenafil (VIAGRA®)

Experimental Gerontology

Volumn 34, Issue 3, 1999, Pages 305-318

  Glossmann, Hartmut ^a   Petrischor, Günther ^b   Bartsch, Georg ^b  

^a A 6020   (Austria)

^b INNSBRUCK MEDICAL UNIVERSITY   (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE; CARBON MONOXIDE; CYCLIC AMP; GUANYLATE CYCLASE; INOSITOL TRISPHOSPHATE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; PHOSPHODIESTERASE; PHOSPHODIESTERASE INHIBITOR; SILDENAFIL;

DRUG ACTIVITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFECT; DRUG HALF LIFE; DRUG MECHANISM; DRUG METABOLISM; DRUG STRUCTURE; ENZYME INHIBITION; PRIORITY JOURNAL; REVIEW; SECOND MESSENGER;

3',5'-CYCLIC-GMP PHOSPHODIESTERASE; AGED; CYCLIC GMP; HUMANS; IMPOTENCE; MALE; NITRIC OXIDE; PHOSPHODIESTERASE INHIBITORS; PIPERAZINES; SIGNAL TRANSDUCTION; VASODILATION;

EID: 0033050763     PISSN: 05315565     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0531-5565(99)00003-0     Document Type: Review

References (55)

1. Andersson K.E., Wagner G. Physiology of penile erection. Physiol Rev. 75:1995;191-236.
2. Anonymous. Sildenafil for erectile dysfunction. Drug Therapeut Bull. 36:1998;81-83.
3. Ballard S.A., Gingell C.J., Tang K., Turner L.A., Price M.E., Naylor A.M. Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. J. Urol. 159:1998;2164-2171.
4. Beavo J.A. Cyclic nucleotide phosphodiesterases functional implications of multiple isoforms . Physiol Rev. 75:1995;725-748.
5. Bloom T.J., Beavo J.A. Identification and tissue-specific expression of PDE7 phosphodiesterase splice variants. Proc Natl Acad Sci USA. 93:1996;14188-14192.
6. Broillet M.C., Firestein S. Direct activation of the olfactory cyclic nucleotide-gated channel through modification of sulfhydryl groups by NO compounds. Neuron. 16:1996;377-385.
7. Burnett A.L. Role of nitric oxide in the physiology of erection. Biol Reprod. 52:1995;485-489.
8. Carter A.J., Ballard S.A., Naylor A.M. Effect of the selective phosphodiesterase type 5 inhibitor sildenafil on erectile dysfunction in the anesthetized dog. J Urol. 160:1998;242-246.
9. + channels in cultured bovine adrenal chromaffin cells. Neurosci Lett. 248:1998;127-129.
10. Chuang A.T., Strauss J.D., Steers W.D., Murphy R.A. cGMP mediates corpus cavernosum smooth muscle relaxation with altered cross-bridge function. Life Sci. 63:1998;185-194.
11. Chuang A.T., Strauss J.D., Murphy R.A., Steers W.D. Sildenafil, a type-5 CGMP phosphodiesterase inhibitor, specifically amplifies endogenous cGMP-dependent relaxation in rabbit corpus cavernosum smooth muscle in vitro. J Urol. 160:1998;257-261.
12. Dent G., White S.R., Tenor H., Bodtke K., Schudt C., Leff A.R., Magnussen H., Rabe K.F. Cyclic nucleotide phosphodiesterase in human bronchial epithelial cells Characterization of isoenzymes and functional effects of PDE inhibitors . Pulm Pharmacol Ther. 11:1998;47-56.
13. Donahue S.P., Taylor R.J. Pupil-sparing third nerve palsy associated with sildenafil citrate (Viagra). Am J Ophthalmol. 126:1998;476-477.
14. European Patent Office (1992). Pyrazolo pyrimidinone antianginal agents. EP 463756A1.
15. Feenstra J., Van Drie-Pierik R.J., Lacle C.F., Strickler B.H. Acute myocardial infarction associated with sildenafil. Lancet. 352:1998;957-958.
16. Fisher D.A., Smith J.F., Pillar J.S., St. Denis S.H., Cheng J.B. Isolation and characterization of PDE9A, a novel human cGMP-specific phosphodiesterase. J Biol Chem. 273:1998;15559-15564.
17. Fisher D.A., Smith J.F., Pillar J.S., St. Denis S.H., Cheng J.B. Isolation and characterization of PDE8A, a novel human cAMP-specific phosphodiesterase. Biochem Biophys Res Commun. 246:1998;570-577.
18. Geng Y., Zhou L., Thompson W.J., Lotz M. Cyclic GMP and cGMP-binding phosphodiesterase are required for interleukin-1-induced nitric oxide synthesis in human articular chondrocytes. J Biol Chem. 273:1998;27484-27491.
19. Goda N., Suzuki K., Naito M., Takeoka S., Tsuchida E., Ishimura Y., Tamatani T., Suematsu M. Distribution of heme oxygenase isoforms in rat liver. Topographic basis for carbon monoxide-mediated microvascular relaxation. J Clin Invest. 101:1998;604-612.
20. Goldstein I., Berman J.R. Vasculogenic female sexual dysfunction vaginal engorgement and clitoral erectile insufficiency syndromes . Int J Impot Res. 10:(Suppl. 2):1998;84-90.
21. Goldstein I., Lue T.F., Padma-Nathan H., Rosen R.C., Steers W.D., Wicker P.A. Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group. N Engl J Med. 338:1998;1397-1404.
22. Gysling E. Sildenafil. Pharma-kritik. 19:1997;75-76.
23. Han P., Zhu X., Michaeli T. Alternative splicing of the high affinity cAMP-specific phosphodiesterase (PDE7A) mRNA in human skeletal muscle and heart. J Biol Chem. 272:1997;16152-16157.
24. Hanson K.A., Ziegler J.W., Rybalkin S.D., Miller J.W., Abman S.H., Clarke W.R. Chronic pulmonary hypertension increases fetal lung cGMP phosphodiesterase activity. Am J Physiol. 275:1998;L931-L941.
25. Ingi T., Ronnett G.V. Direct demonstration of a physiological role for carbon monoxide in olfactory receptor neurons. J Neurosci. 15:1995;8214-8222.
26. Ingi T., Ronnett G.V. Direct demonstration of a physiological role for carbon monoxide in olfactory receptor neurons. J Neurosci. 15:1995;8214-8222.
27. Ingi T., Cheng J., Ronnett G.V. Carbon monoxide An endogenous modulator of the nitric oxide-cyclic GMP signaling system . Neuron. 16:1996;835-842.
28. Jeremy J.Y., Ballard S.A., Naylor A.M., Miller M.A., Angelini G.D. Effects of sildenafil, a type-5 cGMP phosphodiesterase inhibitor, and papaverine on cyclic GMP and cyclic AMP levels in the rabbit corpus cavernosum in vitro. Br J Urol. 79:1997;958-963.
29. Lea A.P., Bryson H.M., Balfour J.A. Intracavernous alprostadil. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in erectile dysfunction. Drugs Aging. 8:1996;56-74.
30. Liu X., Gillespie J.S., Martin W. Non-adrenergic, non-cholinergic relaxation of the bovine retractor penis muscle Role of S-nitrosothiols . Br J Pharmacol. 111:1994;1287-1295.
31. Loughney K., Hill T.R., Florio V.A., Uher L., Rosman G.J., Wolda S.L., Jones B.A., Howard M.L., McAllister-Lucas L.M., Sonnenburg W.K., Francis S.H., Corbin J.D., Beavo J.A., Ferguson K. Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3′,5′-cyclic nucleotide phosphodiesterase. Gene. 216:1998;139-147.
32. Lue, T. F. (1991). Physiology of penile erection. In Jonas et al. (Eds), Erectile Dysfunction. Berlin: Springer-Verlag.
33. Michalets E.L. Update Clinically significant cytochrome P-450 drug interactions . Pharmacotherapy. 18:1998;84-112.
34. Moon C., Jaberi P., Otto-Bruc A., Baehr W., Palczewski K., Ronnett G.V. Calcium-sensitive particulate guanylyl cyclase as a modulator of cAMP in olfactory receptor neurons. J Neurosci. 18:1998;3195-3205.
35. Morales A., Gingell C., Collins M., Wicker P.A., Osterloh I.H. Clinical safety of oral sildenafil citrate (VIAGRA) in the treatment of erectile dysfunction. Int J Impot Res. 10:1998;69-73.
36. Moreland, R. B., Goldstein, I., & Traish, A. (1998). Sildenafil, a novel inhibitor of phosphodiesterase type 5 in human corpus cavernosum smooth muscle cells. Life Sci 62, PL 309-318.
37. Olesen J., Thomsen L.L., Iversen H. Nitric oxide is a key molecule in migraine and other vascular headaches. Trends Pharmacol Sci. 15:1994;149-153.
38. Park K., Goldstein I., Andry C., Siroky M.B., Krane R.J., Azadzoi K.M. Vasculogenic female sexual dysfunction The hemodynamic basis for vaginal engorgement insufficiency and clitoral erectile insufficiency . Int J Impot Res. 9:1997;27-37.
39. Pfeifer A., Klatt P., Massberg S., Ny L., Sausbier M., Hirneiss C., Wang G.S., Korth M., Aszodi A., Andersson K.E., Krombach F., Mayerhofer A., Ruth P., Fassler R., Hofmann F. Defective smooth muscle regulation in cGMP kinase I-deficient mice. EMBO J. 17:1998;3045-3051.
40. Piriev N.I., Shih J.M., Farber D.B. Defective RNA splicing resulting from a mutation in the cyclic guanosine monophosphate-phosphodiesterase beta-subunit gene. Invest Ophthalmol Vis Sci. 39:1998;463-470.
41. Rajfer J., Aronson W.J., Bush P.A., Dorey F.J., Ignarro L.J. Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. N Engl J Med. 326:1992;90-94.
42. Redondo J., Bishop J.E., Wilkins M.R. Effect of atrial natriuretic peptide and cyclic GMP phosphodiesterase inhibition on collagen synthesis by adult cardiac fibroblasts. Br J Pharmacol. 124:1998;1455-1462.
43. Saga M., Mashima Y., Akeo K., Kudoh J., Oguchi Y., Shimizu N. A novel homozygous IIe535Asn mutation in the rod cGMP phosphodiesterase beta-subunit gene in two brothers of a Japanese family with autosomal recessive retinitis pigmentosa. Curr Eye Res. 17:1998;332-335.
44. Soderling S.H., Bayuga S.J., Beavo J.A. Identification and characterization of a novel family of cyclic nucleotide phosphodiesterases. J Biol Chem. 273:1998;15553-15558.
45. Stacey P., Rulten S., Dapling A., Phillips S.C. Molecular cloning and expression of human cGMP-binding, cGMP-specific phosphodiesterase (PDE5). Biochem Biophys Res Commun. 247:1998;249-254.
46. Stief C.G., Uckert S., Becker A.J., Truss M.C., Jonas U. The effect of the specific phosphodiesterase (PDE) inhibitors on human and rabbit cavernous tissue in vitro and in vivo. J Urol. 159:1998;1390-1393.
47. Teixeira C.E., Bento A.C., Lopes-Martins R.A., Teixeira S.A., von Eickestedt V., Muscara M.N., Arantes E.C., Giglio J.R., Antunes E., De Nucci G. Effect of Tityus serrulatus scorpion venom on the rabbit isolated corpus cavernosum and the involvement of NANC nitrergic nerve fibres. Br J Pharmacol. 123:1998;435-442.
48. Trivedi B., Kramer R.H. Real-time patch-cram detection of intracellular cGMP reveals long-term suppression of responses to NO and muscarinic agonists. Neuron. 21:1998;895-906.
49. US Food and Drug Administration, Center for Drug Evaluation and Research. (1998). Review and Evaluation of Pharmacology and Toxicology Data for Sildenafil Citrate.
50. Wang G.R., Zhu Y., Halushka P.V., Lincoln T.M., Mendelsohn M.E. Mechanism of platelet inhibition by nitric oxide in vivo phosphorylation of thromboxane receptor by cyclic GMP-dependent protein kinase . Proc Natl Acad Sci USA. 95:1998;4888-4893.
51. Watanabe N., Kabasawa Y., Takase Y., Matsukura M., Miyazaki K., Ishihara H., Kodama K., Adachi H. 4-Benzylamino-1-chloro-6-substituted phthalazines Synthesis and inhibitory activity toward phosphodiesterase 5 . J Med Chem. 41:1998;3367-3372.
52. Wein, H. J., Van Arsdaten, K., Hanno, Ph. M., & Levin, R. M. (1991). Anatomy of male sexual function. In Jonas et al. (Ed), Erectile Dysfunction. Berlin: Springer-Verlag.
53. Wolfe S.M., Sasich L., Barbehenn E. Safety of sildenafil citrate. Lancet. 352:1998;1393.
54. Zakhary R., Poss K.D., Jaffrey S.R., Ferris C.D., Tonegawa S., Snyder S.H. Targeted gene deletion of heme oxygenase 2 reveals neural role for carbon monoxide. Proc Natl Acad Sci USA. 94:1997;14848-14853.
55. Zhu F.X., Zhang X.Y., Olszewski M.A., Robinson N.E. Mechanism of capsaicin-induced relaxation in equine tracheal smooth muscle. Am J Physiol. 273:1997;997-1001.