Erectile dysfunction (ED) is a common condition where a man is unable to achieve or sustain an erection firm enough for satisfactory sexual performance. While many treatments focus on increasing blood flow to the penis, apomorphine represents a different approach. This medication works not on the penile tissue directly, but by acting on the central nervous system to initiate the neurological cascade necessary for an erection.
How Apomorphine Works
Apomorphine is classified as a dopamine agonist, meaning it mimics the effects of the neurotransmitter dopamine in the brain. The drug works by binding to and stimulating dopamine receptors (D1 and D2 types), which are involved in the brain’s reward and arousal pathways. This stimulation occurs in specific regions of the central nervous system, such as the paraventricular nucleus of the hypothalamus, which is known to be involved in triggering erectogenic signals.
The key distinction of apomorphine is that it initiates the erection process centrally, in the brain, rather than peripherally in the penile tissue. Unlike common first-line treatments for ED, which affect blood vessels to improve blood flow, apomorphine stimulates the neurological desire and arousal pathway. This action helps restore the brain-body connection, particularly in cases of psychogenic ED.
Administration and Dosing for ED
The formulation of apomorphine developed for ED was a sublingual tablet designed to dissolve under the tongue. This route allows the medication to be rapidly absorbed directly into the bloodstream, bypassing the digestive system and liver metabolism. Rapid absorption helps achieve a quick time-to-effect, which is an advantage for on-demand use.
Clinical trials explored a dose-optimization strategy, starting patients on a lower dose and adjusting upward based on efficacy and tolerance. The most effective dosages were 2 milligrams (mg) and 3 mg, with the 3 mg dose offering a favorable balance between effectiveness and side effects. Erections occurred in responsive patients approximately 18 to 23 minutes after administration when sexual stimulation was present.
Clinical Results and Adverse Effects
Clinical studies assessed the effectiveness and safety of apomorphine sublingual tablets in men with ED. Efficacy was measured by the percentage of attempts resulting in an erection firm enough for successful sexual intercourse. Results showed that the 3 mg dose improved the rate of successful intercourse attempts to between 39% and 49%, compared to a baseline rate of 13% to 24% before treatment.
The efficacy was considered modest compared to the superior response rates of PDE5 inhibitors, which show a much higher rate of successful attempts. The most frequent adverse event was nausea, which was dose-dependent and often diminished with continued use. Other common side effects included headache, dizziness, and occasionally vomiting. Serious adverse events like vasovagal syncope occurred rarely, in less than 0.2% of men.
The Current Role of Apomorphine in ED Therapy
Despite its unique mechanism of action and moderate efficacy, apomorphine formulations for ED are not widely available or prescribed today. The drug faced regulatory challenges and has largely been withdrawn from many markets, primarily due to its side effect profile. Patients found the dose-limiting nausea and vomiting unfavorable.
The widespread success of oral PDE5 inhibitors, such as sildenafil and tadalafil, established a higher standard for efficacy and tolerability. These medications demonstrated superior effectiveness with a more manageable side effect profile. Consequently, apomorphine is relegated to a very limited role, sometimes considered only for individuals who cannot take PDE5 inhibitors or who have a strong psychological component to their ED.