History of Apomorphine
Apomorphine was discovered in 1869 and was used for many years as an emetic (a drug used to induce vomiting). Its value in Parkinson’s disease was recognized as early as 1884. In the 1950s, clinical trials confirmed this original observation. At the time, however, the dopaminergic properties of the drug were still not known. With the introduction of domperidone in 1979, the side effects of dopaminergic agonists like apomorphine could effectively be reduced. Apomorphine is now FDA approved as a subcutaneous injection called Apokyn, which is used as-needed to treat loss of control of body movements in people with advanced Parkinson’s disease. It is not commercially available in the United States in sublingual form, although it is available in this form in other countries. Over many years of research, apomorphine has been tried as a treatment for diverse conditions and is now prescribed for treating erectile dysfunction.
Priapism is when erections occur that are painful, last a long time, and may occur without there being stimulation. Sometimes these erections can be prolonged and painful. One side effect that was noticed in patients taking apomorphine for other conditions was that they would sometimes spontaneously get erections. At higher doses used to treat a condition like Parkinson’s, this can be a negative side effect and cause priapism. However when used at controlled dosages that have been tested for treating erectile dysfunction, apomorphine can produce the ability to get and maintain an erection without it being painful. At the lower doses used sublingually, priapism and unwanted erections are uncommon. Most drugs used to treat ED are what are referred to as PDE5 inhibitors. Apomorphine exerts different effects in the body. Some men who do not respond to PDE5 inhibitors may respond to apomorphine and vice versa.
Benefits of Sublingual Apomorphine for Erectile Dysfunction
Apomorphine is poorly absorbed when taken orally. In fact, close to 0% is bioavailable with this administration method. With sublingual administration, at least 20% is bioavailable. The highest level of bioavailability comes with subcutaneous administration. The FDA approved drug Apokyn contains apomorphine in a subcutaneous injection for treating Parkinson’s disease. The subcutaneous version is likely too high a dose for treating ED, as it may produce unnecessary side effects. For treating erectile dysfunction, sublingual tablets have emerged as the easiest method of administration with the least side effects.
Sublingual tablets avoid first-pass metabolism and result in less nausea than other methods of administration. This method of administration allows the drug to be absorbed through the oral mucosa into the blood stream. Nausea is the primary reason apomorphine treatment is discontinued when used for other indications. Avoiding interaction with food and drugs means that the medication does not need to be taken around meals. Some PDE5 inhibitors (and many drugs that are taken orally) may need to be taken away from food and other drugs when they are administered in tablets or capsules.
Research and Results on Apomorphine for Erectile Dysfunction
Apomorphine has been studied extensively for treating erectile dysfunction. In clinical trials for an approved version that was marketed in Europe called Ixsense, over 5,000 men participated who were treated with apomorphine.
“In all apomorphine SL groups, a significantly higher percentage of patients compared with the placebo group achieved and maintained an erection firm enough for intercourse (48% to 53% versus 35% for placebo, P ≤0.001) and a significantly higher percentage of attempts resulted in intercourse (45% to 51% versus 33%, P ≤0.001). The responses to the questionnaires completed by the patients and partners were similar. Apomorphine SL was well tolerated; nausea, the most common side effect, was dose related and diminished substantially during the second 4-week period at all doses. The dose-optimization schedule resulted in fewer adverse events without impacting efficacy.“Efficacy and safety of fixed-dose and dose-optimization regimens of sublingual apomorphine versus placebo in men with erectile dysfunction. https://www.goldjournal.net/article/S0090-4295(00)00575-6/fulltext
Apomorphine exerts its effects by different mechanisms than PDE5 inhibitors. Sildenafil, the active ingredient in the FDA-approved medication Viagra, prevents the breakdown of cGMP in the corpora cavernosa, thereby improving erection. In contrast, apomorphine’s main site of action is in the central nervous system. This means it works through a central mechanism while sildenafil works through a peripheral mechanism.
Dosing for ED
In most cases, apomorphine should start to work within 20-30 minutes and often sooner. Apomorphine should not be discontinued if it does not work the first time it is taken, unless there are side effects. The success of apomorphine increases over sequential dosages when it is taken correctly. At least 4-6 attempts should be made before the treatment is considered unsuccessful. Doses are often titrated up from 2mg to 3mg so the body can become adjusted to the drug. Increasing to 4mg is generally not recommended as the benefits are about the same as the 3mg dose but the side effects are increased. In comparison trial, it was found that: “The 3–mg dose was not significantly different from 4 mg in the evaluation of efficacy variables, but the incidence of adverse events was higher with 4 mg. Nausea was the most common event, reported by 3.3% of patients on 3 mg vs. 14.1% on 4 mg.”
Many men with ED will respond to treatment with apomorphine. However it will not work for all men. Some may require a combination of other treatments or may prefer to use PDE5 inhibitors like sildenafil, tadalafil, or vardenafil. There are also multiple aspects of ED that need to be considered when deciding on treatments. Aspects of stress, anxiety, and other psychological issues frequently contribute to erectile dysfunction. Psychosocial therapy using behavioral or cognitive-behavioral approaches have been shown to be effective at helping resolve sexual concerns. Certain pre-existing health conditions also can affect the ability to maintain an erection. Prescribers should consider all of these possible factors when deciding on treatments for their patients.
Nausea is a potential side effect of apomorphine that must be considered. It has a history of being used as an emetic. When used to treat Parkinson’s disease, it is always combined with an anti-emetic. This side effect will not be as pronounced when using apomorphine sublingually but some men will still experience nausea. With continued use, the body can adjust to apomorphine and side effects tend to diminish. Patients with cardiac disease may be at an increase risk of complications and should take any erectile dysfunction drug with caution and careful consultation with their healthcare provider. All patients should minimize their alcohol intake when taking apomorphine as the combination may significantly reduce blood pressure. In addition, alcohol may negatively affect sexual performance regardless of whether apomorphine or another drug is used.
The role of apomorphine SL in the treatment of male erectile dysfunction – BJU International
Efficacy and safety of fixed-dose and dose-optimization regimens of sublingual apomorphine versus placebo in men with erectile dysfunction – Adult Urology
Absorption of apomorphine by various routes in parkinsonism. – Official Journal of the Movement Disorder Society
Double–Blind, Crossover Comparison of 3 mg Apomorphine SL with Placebo and with 4 mg Apomorphine SL in Male Erectile Dysfunction – European Urology
Safety and tolerability of apomorphine SL in patients with erectile dysfunction – BJUI International