Apomorphine for Erectile Dysfunction: How It Works and What the Evidence Shows

Most men who have looked into erectile dysfunction treatment have heard of the pill-based medicines that work on blood flow in the penis. Apomorphine is far less familiar, because it takes a different route entirely: it acts in the brain, on the signals that start an erection in the first place. It was studied for ED in the late 1990s and early 2000s, approved for a time in Europe, and then largely set aside. This guide explains how it works, what those studies found, and the safety points that come with it.

A medicine that works in the brain

Apomorphine is a dopamine agonist, meaning it mimics dopamine, a chemical messenger in the brain. Despite the name, it is not related to morphine and is not an opioid.

An erection is not purely a local event. Areas of the hypothalamus, a region deep in the brain, help coordinate sexual response and send signals down the spinal cord to the nerves of the penis. Apomorphine is thought to stimulate dopamine receptors in these hypothalamic centers, which helps trigger that cascade. Much of the detailed understanding, including the role of dopamine-sensitive nerve cells in a structure called the paraventricular nucleus, comes from animal studies, so the exact mechanism in men is less certain than for medicines that act on blood vessels.

This is a different mechanism from tadalafil and other PDE5 inhibitors, which amplify the blood-flow step once arousal has started. Our guide to how tadalafil works covers that side of the process.

How it was taken

Swallowed apomorphine is largely broken down by the liver before it reaches the bloodstream, leaving under 4% available. For that reason, the ED versions were designed as tablets that dissolve under the tongue, where the medicine can be absorbed through the lining of the mouth directly into the circulation.

What the trials showed

The ED studies tested sublingual doses between 2 mg and 6 mg, with most of the evidence at 2 to 4 mg.

• Speed of onset. In a crossover trial of 296 men, the median time to an erection on 3 mg was about 19 minutes. Reviews describe the onset as roughly 20 minutes.
• Effect versus placebo. In that same trial, 3 mg produced erections firm enough for intercourse more often than placebo, as rated by both men and their partners. A 4 mg dose was no better than 3 mg but caused more side effects.
• Size of the benefit. A 2020 meta-analysis of nine randomized trials found apomorphine increased successful attempts by roughly 6 to 27 percentage points over placebo. That is a real but modest effect.
• Compared with PDE5 inhibitors. In head-to-head comparisons, a PDE5 inhibitor worked better than apomorphine and was preferred by most men.
• Groups where it helped less. The meta-analysis found no significant benefit after radical prostate surgery, and a study in men with diabetes did not show a significant difference from placebo.

Taken together, apomorphine helped some men, worked quickly, and was generally weaker than the medicines that act on blood flow. That helps explain why it never became a first-line ED treatment.

The 1 mg question

Every published ED trial used at least 2 mg. A 1 mg dose of apomorphine is below the range that was studied, and there is no clinical evidence that 1 mg on its own improves erections. When apomorphine at low doses appears in a combination product, its contribution at that dose has not been measured in trials. The guide to tadalafil and apomorphine together looks at what that means.

Regulatory history

Apomorphine's path through the regulators is part of the picture:

• Europe. Sublingual apomorphine tablets for ED were authorised in the European Union in 2001. Both products were later withdrawn, one for commercial reasons in 2004 and the other when its authorisation lapsed in 2006.
• United States. Apomorphine has never been approved by the FDA for erectile dysfunction. An application was withdrawn in 2000, after an advisory committee raised concerns about fainting and low blood pressure.
• Current US approvals. The forms of apomorphine approved in the US today are for Parkinson's disease, to treat sudden "off" episodes, and use much higher doses than were studied for ED.

Side effects

Nausea is the side effect most associated with apomorphine:

• At 3 mg, about 7% of men reported nausea, compared with about 1% on placebo. At 4 mg it rose to about 14%.
• In a dose-escalation study from 2 to 4 mg, dizziness affected about 7% and headache about 7%.
• Fainting was rare at the doses studied, but it was the concern that shaped the medicine's regulatory history. It is more likely with higher doses, alcohol, dehydration or blood pressure medicines.

Our side effects guide covers these alongside the effects of tadalafil.

Interactions to know about

The most important interaction is with a group of anti-nausea medicines called 5-HT3 antagonists, which includes ondansetron and granisetron. Taken with apomorphine, they have caused severe drops in blood pressure and loss of consciousness, so the combination is contraindicated. This matters in everyday life, because ondansetron is commonly given for stomach bugs, after surgery and during chemotherapy. If a doctor or pharmacist offers you an anti-nausea medicine, tell them you take apomorphine.

Alcohol, blood pressure medicines and nitrates can all add to apomorphine's blood-pressure-lowering effect. The full picture, including the strict rule on nitrates for any ED medicine, is in our ED medication safety guide.

When to get urgent help

Stop and get emergency care if you faint or feel close to fainting and do not recover quickly, have chest pain, have an erection lasting more than four hours, or notice a sudden change in your vision or hearing. If you were given any anti-nausea medicine recently, mention it.

What this means in practice

Apomorphine is a genuinely different tool: it acts centrally, works quickly, and has modest evidence of benefit at 2 to 3 mg. It also carries a nausea and fainting profile that needs respect, and it has no FDA approval for ED. Anyone considering a product that contains it should expect a physician to review their blood pressure, heart health and current medicines first, and should know where the evidence is strong and where it is thin.

Sources

1. Dula E, et al. Double-blind crossover comparison of 3 mg apomorphine SL with placebo and 4 mg. Eur Urol 2001
2. Guillén V, et al. Apomorphine for the treatment of erectile dysfunction: systematic review and meta-analysis. Arch Sex Behav 2020
3. Sublingual apomorphine for the treatment of erectile dysfunction (review). Expert Opin Investig Drugs 2002
4. Apomorphine sublingual film prescribing information, FDA (2020)
5. Apomorphine sublingual versus subcutaneous pharmacokinetics (2021)

Related reading

• Erectile dysfunction overview: the main causes and treatment approaches in one place.
• How tadalafil works: the blood-flow side of the erection, and daily low-dose use.
• Tadalafil and apomorphine together: why the two are combined and what the evidence does and does not show.
• ED medication safety: who should not take ED medicines and which interactions matter.
• Performance anxiety and ED: the mental side of erections and how it interacts with medication.

This article is for education only and is not a substitute for professional medical advice. Do not start, stop or change a medication without speaking to a licensed clinician. If you have chest pain, an erection lasting more than four hours, or sudden loss of vision or hearing, seek emergency care.