How apomorphine works
Apomorphine mimics the neurotransmitter dopamine in the central nervous system and binds to its docking sites (receptors). In this way, the active ingredient mediates the effects typical of dopamine.
Parkinson’s disease:
In Parkinson’s disease, nerve cells that produce and secrete dopamine gradually die. The use of apomorphine can therefore be helpful. However, the active ingredient is usually only used when the therapy options with fewer side effects have been exhausted.
These include better-tolerated dopamine agonists and the active ingredient L-dopa, a precursor substance of dopamine that the body can convert to dopamine. L-dopa therapy can be administered for an average of about ten years before so-called on-off phenomena occur.
As before, a constant amount of L-dopa is administered, but the effectiveness fluctuates drastically – one day the drug works well, the next day hardly at all. These fluctuations become more pronounced until at some point L-dopa is barely effective. At this point, therapy can be started with apomorphine, which is sometimes considered the last treatment option.
The so-called apomorphine test is sometimes used to diagnose Parkinson’s disease. In this test, the patient is injected with the active substance to see whether the movement disorders typical of the disease can be alleviated.
Erectile dysfunction:
During Parkinson’s treatment with apomorphine, it was discovered by chance that male patients with potency disorders could regain an erection. As a result, the active ingredient was also marketed for some years as a remedy for potency disorders. However, due to insufficient sales figures, the preparations in question were then taken off the market again.
Emetic:
In emergency medicine and veterinary medicine, apomorphine is additionally used as a reliable agent to induce emesis (emetic) – but outside its approval (“off-label use”).
Although apomorphine is chemically a derivative of morphine, it has no analgesic or other effects that one would expect from a morphine derivative.
Uptake, degradation and excretion
Apomorphine is usually injected, which allows it to enter the systemic circulation very quickly. As a result, its effect usually sets in within less than ten minutes. The active ingredient is then rapidly broken down (partially in the liver) and excreted through the kidneys. The time after which half of apomorphine has left the body again (half-life) is approximately half an hour.
When is apomorphine used?
Apomorphine is officially approved for the following indications:
- Treatment of motor fluctuations (“on-off” phenomenon) in patients with Parkinson’s disease who cannot be adequately controlled by orally administered antiparkinsonian drugs.
Use for potency disorders or as an emetic may be with available preparations outside the scope of marketing authorization (“off-label use”) or with imported finished drugs.
The duration of use depends on the underlying disease.
How apomorphine is used
The apomorphine preparations available in Germany, Austria and Switzerland are only suitable for injection or infusion (also for continuous infusion by means of a pump). Pre-filled syringes and pre-filled pens (similar to insulin pens) are available for this purpose, so that patients can also inject themselves with the active substance after being instructed by a physician.
At the beginning, the individually suitable dosage must be determined: In principle, it can be one to one hundred milligrams of apomorphine per day; the average is 3 to 30 milligrams per day. However, no more than ten milligrams of the active substance may be administered per single dose.
In addition, another agent is generally given (usually domperidone) to suppress severe nausea (apomorphine side effect).
The use of apomorphine for potency disorders is usually as a sublingual tablet. This is a tablet that is placed under the tongue, where it dissolves quickly. With this form of administration, the desired effect occurs sufficiently quickly, while the side effects are usually very low.
What are the side effects of apomorphine?
One in ten to one hundred patients experience side effects in the form of confusion, hallucinations, sedation, drowsiness, dizziness, lightheadedness, frequent yawning, nausea, vomiting, and reactions at the injection site such as redness, tenderness, itching, and pain.
Occasionally, there is skin damage at the injection site, rashes, difficulty breathing, drop in blood pressure when standing up from a lying or sitting position, movement disorders, and anemia.
What should be considered when using apomorphine?
Contraindications
Apomorphine must not be used in:
- Hypersensitivity to the active substance or to any of the other ingredients of the drug.
- impaired respiratory control (respiratory depression)
- Dementia
- Psychosis
- Liver dysfunction
- Patients who respond to L-dopa administration with an “on-period,” i.e., movement disorders (dyskinesias) or involuntary muscle contractions (dystonias)
Interactions
During treatment with apomorphine, active substances against psychosis and schizophrenia (antipsychotics) should not be taken. These act as dopamine antagonists, i.e. in the opposite direction to apomorphine. With simultaneous use, it can therefore be assumed that at least one active ingredient is not sufficiently effective.
Antihypertensive drugs may have an increased antihypertensive effect when used concomitantly with apomorphine.
Agents that slow down the conduction of impulses in the heart (more precisely: prolong the so-called QT interval) must not be combined with apomorphine, as this can lead to life-threatening cardiac arrhythmias. Examples are certain drugs against depression (amitriptyline, citalopram, fluoxetine), antibiotics (ciprofloxacin, azithromycin, metronidazole) and drugs against fungal infections (fluconazole, ketoconazole).
Age restriction
Apomorphine is contraindicated in children and adolescents under 18 years of age.
Pregnancy and lactation
No data are available on the use of apomorphine in pregnant women. At least in animal studies, there were no indications of a fertility-endangering and fertility-damaging effect (reproductive toxicity). However, since these results are not easily transferable to humans, it is recommended according to the expert information not to use apomorphine in pregnant women.
It is not known whether apomorphine passes into breast milk. A risk for breastfeeding infants can therefore not be ruled out. Experts therefore recommend that the attending physician and the mother decide together whether the treatment should be continued (possibly while breastfeeding) or terminated.
How to get medication with apomorphine
Preparations containing the active ingredient apomorphine are subject to prescription in Germany, Austria and Switzerland in any dosage and dosage form.
How long has apomorphine been known for?
As early as 1869, chemists Augustus Matthiessen and Charles Wright were able to obtain a new substance they called apomorphine by boiling pure morphine – a strong painkiller – in concentrated hydrochloric acid.
However, this has a completely different effect from the original substance. Instead of being used as a painkiller, apomorphine was therefore first introduced into medicine as a strong emetic.
