What is Sildenafil?
Sildenafil is the best-known PDE-5 inhibitor and became world-famous under the brand name Viagra. It is used for erectile function and is one of the most studied compounds there is.
It is taken as a tablet on demand, about half an hour to an hour before the desired effect. Sildenafil works relatively fast over a medium time window, which makes it the classic "shortly before" option.
How it works
An erection happens when a messenger (cGMP) relaxes the blood vessels in the penis so more blood flows in. The enzyme PDE-5 breaks that messenger down again. Sildenafil blocks PDE-5, so the signal lasts longer and the erection comes more easily and stays more stable.
Important: sildenafil does not replace sexual arousal, it only amplifies the natural response. Without stimulation, nothing happens.
Where it acts
Where sildenafil acts
Tap a point or a card. Colour = PDE5, grey = observed in studies.
- Erectile tissue and vessels
More cGMP, smooth muscle relaxes, more blood flows in2
PDE5 - Eye
Colour tinge in vision, because PDE6 of the retina is also slightly inhibited2
Observed in trials - Head
Headache in 16 versus 4 percent2
Observed in trials - Stomach
Indigestion in 7 versus 2 percent2
Observed in trials - Liver
Breakdown mainly via CYP3A4, an active breakdown product forms2
Observed in trials
Targets in the ChEMBL database4
Compound CHEMBL1737: one recorded mechanism, Inhibitor, direct binding.
- Gene
- PDE5A
- UniProt
- O76074
- ChEMBL
- CHEMBL1827
- Action
- Inhibitor, direct binding
How to take it
Sildenafil is swallowed as a tablet, about 30 to 60 minutes before activity.
- A fatty meal noticeably delays and weakens the effect. So take it with some gap from food, ideally on a fairly empty stomach.
- At most once a day.
- Larger amounts of alcohol can worsen the effect.
Sildenafil vs Tadalafil
The two most-compared PDE-5 inhibitors. The core difference is duration:
- Sildenafil lasts about 4 to 6 hours, fast onset, classically taken shortly before. More sensitive to fatty food.
- Tadalafil lasts up to 36 hours (the "weekend pill") and decouples dosing in time from activity. Less sensitive to food, can also be dosed low daily.
In short: sildenafil for planned, single occasions, tadalafil for more spontaneity over a longer window. Which fits better is individual.
Comparison
Four PDE5 inhibitors in the lexicon
All four inhibit the same enzyme. They differ mainly in how fast they act and for how long, as stated in the TPD lexicon. Tap a card to open its entry.
Simplified: sildenafil acts for a few hours, tadalafil considerably longer. 42
What the research shows
Sildenafil is extremely well evidenced. In the approval study (Goldstein, 1998), the success rate rose clearly with dose, with about 69 percent of attempts successful in the dose-escalation group versus 22 percent on placebo. On this basis sildenafil was approved and has since been studied and used millions of times.
The study with a link is in the source block below.
Study results
What the trials measured
Interactive: switch tabs, tap points, show or hide arms. Arms are named relative to each other, no dosing advice.
Share of successful attempts1
329 men, flexible dose escalation over 12 weeks, last four weeks
Per month an average of 5.9 instead of 1.5 attempts succeeded. In the second study with 532 men erection improved with increasing dose, 92 percent completed the following open-label extension.
Research status
Where the research stands
Sildenafil has been approved since 1998. On ClinicalTrials.gov 494 trials list sildenafil among their interventions, also on questions other than erection. The approval study ran before the registry. Shown are three completed post-approval trials. As of 26 Oct 2026. 3
- Preclinical Principle: inhibition of phosphodiesterase 5
- Phase 1 no registered trial
- Phase 2 no registered trial
- Phase 3 no registered trial
- Approval since 1998
Show all 3 phase 4 trials on a timelineHide timeline
NCT00143221 · 350 participants, started Mar 2004, primary endpoint reached May 2005.
Registry entry ↗ · Results not yet in PubMed
NCT00143260 · 250 participants, started Aug 2005, primary endpoint reached May 2006.
Registry entry ↗ · Results not yet in PubMed
NCT00301262 · 183 participants, started Nov 2005, primary endpoint reached Sept 2007.
Registry entry ↗ · Results not yet in PubMed
Bar: start to primary endpoint (planned for running trials). Green = completed, blue = progress until 26 Oct 2026.
Side effects
The most common effects are mild and come from the mechanism: headache, facial flush, a stuffy nose, sometimes heartburn. Occasionally a blue-tinged or blurred vision that passes. Most effects are dose-dependent.
Tolerability
Side effects compared with placebo
Out of 100 participants per group, how many had the event over 2 to 26 weeks.
| Event | Placebo | Sildenafil |
|---|---|---|
| Headache2 | 4% | 16% |
| Flushing2 | 1% | 10% |
| Indigestion2 | 2% | 7% |
| Nasal congestion2 | 2% | 4% |
| Abnormal vision2 | 0% | 3% |
| Abnormal vision by fixed dose2 | 1% | 0% |
The visual disturbance was mostly a colour tinge, more light sensitivity or blurred vision, mild and transient. Discontinuation due to side effects was 2.5 percent on sildenafil and 2.3 percent on placebo.2
Safety and interactions
One point is non-negotiable and the most important here: PDE-5 inhibitors must never be combined with nitrates. That includes heart nitrates (e.g. nitroglycerin) and also "poppers" (amyl nitrite). The combination can drop blood pressure dangerously.
Caution also with alpha-blockers (blood pressure) and with existing cardiovascular disease. Anyone with pre-existing conditions or on medication should clear it with a doctor first. This is not an area for experiments.
Storage
Store the tablets dry, at room temperature and protected from light, out of reach of children. Keep the original packaging closed and mind the expiry date.
