What is the mechanism of action (MOA) of Alprostadil?

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Last updated: March 18, 2025 • View editorial policy

From the Guidelines

The mechanism of action of alprostadil involves direct vasodilation through relaxation of smooth muscle in blood vessels, as it is a synthetic form of prostaglandin E1 (PGE1) that works by binding to specific receptors on vascular smooth muscle cells, activating adenylate cyclase, which increases intracellular cyclic adenosine monophosphate (cAMP) levels. This biochemical cascade leads to decreased intracellular calcium concentration, resulting in smooth muscle relaxation and vasodilation. In clinical applications, alprostadil is used to treat erectile dysfunction (when injected into the penis or applied as a urethral suppository), to maintain patency of the ductus arteriosus in neonates with certain congenital heart defects (intravenous administration), and to improve blood flow in peripheral vascular disease, as noted in the 2018 erectile dysfunction guideline 1. The vasodilatory effects occur rapidly after administration, with duration varying by route of administration. Some key points to consider when using alprostadil include:

  • It is the only FDA-approved medication for intracavernous injection (ICI) therapy in the U.S. 1
  • It can be used as monotherapy or in combination with other vasoactive drugs, such as papaverine and phentolamine, for the treatment of erectile dysfunction 2
  • The initial trial dose of alprostadil intra-urethral suppositories should be administered under healthcare provider supervision due to the risk of syncope 3 Side effects are primarily related to its vasodilatory properties and can include hypotension, flushing, and pain at the application site. Overall, alprostadil is a effective treatment option for various conditions, including erectile dysfunction, and its mechanism of action is well-established as a direct vasodilator.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Alprostadil (prostaglandin E1) is one of a family of naturally occurring acidic lipids with various pharmacologic effects. Vasodilation, inhibition of platelet aggregation, and stimulation of intestinal and uterine smooth muscle are among the most notable of these effects Smooth muscle of the ductus arteriosus is especially sensitive to alprostadil, and strips of lamb ductus markedly relax in the presence of the drug

The mechanism of action (MOA) of Alprostadil is through its effects as a prostaglandin E1, which include:

  • Vasodilation
  • Inhibition of platelet aggregation
  • Stimulation of smooth muscle Specifically, Alprostadil causes relaxation of smooth muscle in the ductus arteriosus. 4

From the Research

Mechanism of Action of Alprostadil

  • Alprostadil is a vasodilating agent that acts by relaxing the smooth muscles of the corpus cavernosum and increasing the diameter of cavernous arteries, leading to erection 5, 6
  • The mechanism of alprostadil involves the relaxation of smooth muscles and the increase of blood flow to the penis, resulting in an erection 5, 6

Pharmacokinetics and Pharmacodynamics

  • Following intracavernous administration, alprostadil is either locally metabolized or rapidly cleared from the penis into the systemic circulation, where it is extensively metabolized by the lungs 5
  • Alprostadil has a favorable pharmacodynamic profile, with poor absorption into systemic circulation, making it suitable for treatment of erectile dysfunction with reduced risk of adverse effects 7

Clinical Efficacy

  • Alprostadil has been shown to be effective in inducing erections in patients with erectile dysfunction, with efficacy rates of up to 70% in short-term studies 5, 6
  • Clinical trials have demonstrated the efficacy of alprostadil in treating erectile dysfunction, with significant improvements in erectile function and quality of life 8, 7

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.