Phosphodiesterase 5 inhibitors: preclinical and early-phase breakthroughs for impotence treatments

ABSTRACT

Introduction

Erectile dysfunction (ED) is a condition that affects millions of men worldwide and is characterized by the inability to achieve or maintain an erection for satisfactory sexual performance. There are numerous treatment options for ED, including medications, mechanical assist devices, and surgical management; however, first-line treatment is usually a phosphodiesterase 5 (PDE5) inhibitor. There is a growing interest in developing novel, efficacious PDE5 inhibitors that provide better quality, safety, and tolerability profiles with less adverse effects. Our review of udenafil, mirodenafil, youkenafil, lodenafil, and SLx-2101 analyzes the safety, efficacy, and pharmacokinetic properties of these new ED drugs.

Areas covered

Clinical trials demonstrated improved scores in questionnaires, such as the International Index of Erectile Function and Sexual Encounter Profile, for udenafil, mirodenafil, and lodenafil, while youkenafil and SLx-2101 revealed enhanced safety and tolerability in early pharmacokinetic studies.

Expert opinion

It is our opinion that more robust clinical trials are required before these medications can be made available in the United States. Additionally, the field of urology may benefit from pursuing other avenues of pharmacotherapy, such as injections, tablets with a different mechanism of action, or stem cell therapy, to restore the integrity of the endothelium within the penis.

KEYWORDS:

• Erectile dysfunction
• phosphodiesterase inhibitors
• adverse events
• novel drugs
• pharmacokinetics

Article highlights

• Erectile dysfunction (ED) is a common patient complaint worldwide.

• First-line treatment therapies for ED may lead to adverse effects that cause intolerance or nonadherence

• Novel phosphodiesterase 5 (PDE5) inhibitors have recently been developed and trialed to assess their efficacy, safety, and tolerability in men

• Our review covers current literature on new PDE5 inhibitors, including udenafil, mirodenafil, youkenafil, lodenafil, and SLx-2101

• We review their pharmacokinetic properties and the results of clinical trials for these novel agents

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors wish to thank Dr. Scott Bailey, Department of Urology, Tulane University School of Medicine, for editing and preparing this manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Author contributions

Z Melchiode, T Nguyen, O Dawood, and GA Bobo performed literature searches, Z Melchiode, T Nguyen, O Dawood, and GA Bobo drafted the manuscript, and Z Melchiode, O Dawood, GA Bobo, and WJG Hellstrom revised and finalized the manuscript for publication.

Additional information

Funding

This manuscript was not supported by any funding.