Products
Uprima sublingual tablets (2 mg, 3 mg) for erectile dysfunction are no longer marketed in many countries. The marketing authorization was not renewed by Abbott AG in 2006. Commercial reasons were cited, probably attributed to competition from phosphodiesterase-5 inhibitors (e.g., sildenafil, Viagra). It is also possible that a post-marketing study had played a role, calling into question the efficacy (Maclennan et al., 2006). Injectable solutions are also approved in many countries for the treatment of PD.
Structure and properties
Apomorphine (C17H17NO2, Mr = 267.3 g/mol) is a lipophilic morphine derivative without opioid effects that can be obtained by heating morphine with acid. It is structurally similar to dopamine. The salt apomorphine hydrochloride (-apomorphine – HCl – 1/2 H2O) is present in the form of crystals that are white, faint yellowish brown, or gray with a green tinge and are sparingly soluble in water. It turns green with time when exposed to air and light. By definition, apomorphine hydrochloride is the -enantiomer. The -enantiomer is a .
Effects
Apomorphine (ATC G04BE07) is proerectile, emetic, dopaminergic, and hypotensive. Unlike phosphodiesterase-5 inhibitors, the erectile effect is achieved by a central mechanism. Apomorphine binds to dopamine receptors in the hypothalamus and, via a neuronal cascade, eventually leads to relaxation of smooth muscle in the corpus cavernosum of the penis, allowing improved blood filling and erection. Sexual stimulation is necessary. Apomorphine has a low oral bioavailability due to a high first-pass metabolism and is therefore administered as a sublingual tablet via the oral mucosa, which allows a rapid onset of action within approximately 20 minutes. Due to its high lipophilicity, it crosses the blood–brain barrier well. Apomorphine has been tested in clinical trials with over 5000 participants. We cannot comment on the actual efficacy. Dopamine agonists are known from Parkinson’s therapy to trigger behavioral disorders such as obsessive-compulsive behavior, hypersexuality and gambling addiction. Therefore, one could assume that these effects also play a role in the application against erectile dysfunction. However, according to the scientific literature, this is not the case. Apomorphine does not appear to have any effect on libido-at least at the low doses used-that is, it does not promote sex drive, alter behavior, or trigger psychological disorders (e.g., Dépatie, Lal, 2001).
Indications
Apomorphine was used for erectile dysfunction in men. The drug was not intended for use in women. Apomorphine is also used medically to treat Parkinson’s disease and to induce vomiting.
Dosage
According to the drug label. The usual dose is 2 mg but may be increased to 3 mg. At least 8 hours must elapse before taking another dose. The sublingual tablet is placed under the tongue 20 minutes before sexual activity. A small amount of water should be drunk.
Contraindications
Apomorphine is contraindicated in hypersensitivity, severe unstable angina, recent myocardial infarction, severe heart failure or hypotension, and other conditions that make sexual activity inadvisable. For complete precautions, see the drug label.
Interactions
Apomorphine is mainly conjugated and interactions via CYP seem unlikely. Combination with nitrates is not recommended because of the potential for increased blood pressure lowering. No interactions were found with other antihypertensive agents studied; nevertheless, caution is advised. Interactions are possible with dopamine agonists and dopamine antagonists. Concurrent use is not recommended. Alcohol may decrease sexual performance and lead to an increased decrease in blood pressure. For full details, see the drug label.
Adverse effects
The most common adverse effects include nausea – apomorphine is also used as an emetic at higher doses – headache, and dizziness.Other possible side effects include: Inflammation of the nasal or pharyngeal mucosa, yawning, drowsiness, infection, pain, coughing, flushing, sweating, taste disturbances, indigestion, vaso-vagal syndrome with fainting and brief unconsciousness, and ulcers in the mouth and hypersensitivity reactions.
Cf.
Dopamine agonists, phosphodiesterase-5 inhibitors, erectile dysfunction.