Molecular mechanisms and pharmacokinetics of phosphodiesterase-5 antagonists

被引：65

作者：

Sharron H. Francis

Jackie D. Corbin

机构：

[1] Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Light Hall Room 702, Nashville, 37232-0615, TN

来源：

Current Urology Reports | 2003年 / 4卷 / 6期

关键词：

Allosteric Site; Cyclic Nucleotide; Erectile Dysfunction; Tadalafil; Vardenafil;

D O I：

10.1007/s11934-003-0027-x

中图分类号：

学科分类号：

摘要：

The prominence of phosphodiesterase-5 (PDE-5) inhibitors in the treatment of male erectile dysfunction and other diseases related to vascular dysfunction mandates a comprehensive understanding of the properties and effects of these compounds. Three potent and selective PDE-5 inhibitors (sildenafil, tadalafil, and vardenafil) have been approved for clinical use. The clinical efficacy and safety profiles of these medications are related to their molecular mode of action, the selectivity for PDE-5, and the pharmacokinetic properties (absorption, bioavailability, time to onset of action, distribution, metabolism, and elimination). These PDE-5 inhibitors share some common properties with regard to mechanisms of action and selectivities for PDE-5. They also have distinctive characteristics that may impact their clinical use. This article focuses on the basic biochemistry of cyclic guanosine monophosphate signaling and the pharmacokinetic parameters that describe characteristics of drug action of these PDE-5 inhibitors in facilitating smooth muscle relaxation, leading to improved penile erectile response or causing side effects. © 2003, Current Science Inc.

引用

页码：457 / 465

页数：8

共 51 条

[1]

Robison G.A., Butcher R.W., Sutherland E.W., Cyclic AMP, (1971)

[2]

Burns F., Zhao A.Z., Beavo J.A., Cyclic nucleotide phosphodiesterases: gene complexity, regulation by phosphorylation, and physiologic implications, Adv Pharmacol Academic Press, 36, pp. 29-48, (1996)

[3]

Corbin J.D., Francis S.H., Cyclic GMP phosphodiesterase-5: target for sildenafil, J Biol Chem, 274, pp. 13729-13732, (1999)

[4]

Francis S.H., Turko I.V., Corbin J.D., Cyclic nucleotide phosphodiesterases: relating structure and function, Prog Nucleic Acid Res Mol Biol, 65, pp. 1-52, (2001)

[5]

Soderling S.H., Beavo J.A., Regulation of cAMP and cGMP signaling: new phosphodiesterases and new functions, Curr Opin Cell Biol, 12, pp. 174-179, (2000)

[6]

Jeremy J.Y., Ballard S.A., Naylor A.M., Et al., 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, pp. 958-963, (1997)

[7]

Ballard S.A., Gingell C.J., Tang K., Et al., 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, pp. 2164-2171, (1998)

[8]

Corbin J.D., Francis S.H., Pharmacology of phosphodiesterase-5 inhibitors, Int J Clin Pract, 56, pp. 453-459, (2002)

[9]

Rotella D.P., Phosphodiesterase 5 inhibitors: current status and potential applications, Nat Rev Drug Discov, 1, pp. 674-682, (2002)

[10]

Hellstrom W.J., Gittelman M., Karlin G., Et al., Vardenafil for treatment of men with erectile dysfunction: efficacy and safety in a randomized, double-blind, placebo-controlled trial, J Androl, 23, pp. 763-771, (2002)

← 1 2 3 4 5 6 →