An overview of conventional and investigational phosphodiesterase 5 inhibitors for treating erectile dysfunction and other conditions

ABSTRACT

Introduction

There is a rising concern about developing innovative, efficacious PDE5I molecules that provide better safety, efficacy and tolerability with less adverse effects. Innovative PDE5I with dual targets have also been defined in the literature. Additionally, some of PDE5I are able to selectively inhibit other enzymes such as histone deacetylase, acetylcholine esterase, cyclooxygenase or act as nitric oxide donors. This review presents knowledge concerning the advanced trends and perspectives in using PDE5I in treatment of ED and other conditions.

Areas Covered

Pre-clinical and early clinical trials that investigated safety, efficacy and tolerability of novel PDE5I such as Udenafil, Mirodenafil, Lodenafil, Youkenafil, Celecoxib and TPN729 in treatment of ED and other conditions.

Expert Opinion

Preclinical and limited early clinical studies of the new molecules of PDE5I have demonstrated encouraging results however, safety, efficacy, and tolerability are still an issue that necessitate further long-term multicenter clinical studies to ensure justification of their uses in treatment of ED and other conditions.

Progress in molecular delivery techniques and tailored patient-specific management and additional therapeutic technology will dramatically improve care for ED and other conditions. The dream of ED and many other conditions becoming more effectively managed may be feasible in the near future.

KEYWORDS:

• PDE5I
• Erectile dysfunction
• Impotence
• LUTS

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Article highlights:

• There is increasing concern about the need to develop new, potent PDE5I drugs that have better safety, efficacy, acceptance and fewer side effects.

• The review provides a brief overview of PDE5I mechanism of action.

• PDE5I are used in several routes, including oral (FDA-approved and next generation non-FDA-approved), orally dispersible pills, and topically, which are all commonly used.

• Innovative developments in PDE5I medication technology are highly encouraging and should yield new, potent PDE5I medications in the future

• PDE5I have been studied by several researchers in a wide range of therapeutic situations outside of their known use in management of erectile dysfunction.

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.

Reviewer disclosures

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

Author contribution

AI Elsakka and EA Ismail participated with the review’s concept and design. The initial draft of the review was written by AI Elsakka. Parts of the review were written by EA Ismail. Each author reviewed and approved the submitted version of the manuscript and participated in its editing.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13543784.2024.2388569

Additional information

Funding

This paper was not funded.