Pergolide is an active ingredient isolated from naturally occurring fungal alkaloids and is approved as a therapeutic agent for Parkinson’s disease. It is also used in veterinary medicine for the treatment of an equine disease. Pergolide acts on the receptors of the neurotransmitter dopamine.
What is pergolide?
Pergolide drugs are used as a monopreparation for long-term therapy of Parkinson’s disease. Pergolide has the molecular formula C19H26N2S and is a dopamine agonist. The active ingredient is produced by a tubular fungus that lives as a parasite on certain types of grain. The ergot alkaloid is related to ergotamine, which is used to treat acute, prolonged migraine attacks. Pergolide drugs are used as a monopreparation for long-term therapy of Parkinson’s disease (primary and secondary syndrome). Parkinson’s disease is a neuro-degenerative disease, mostly age-related, which progresses slowly. In the incurable disease, mainly the nerve cells of the substantia nigra die. It is located in the midbrain. Its nerve cells are responsible for the production of the neurotransmitter dopamine. The most important symptoms of Parkinson’s disease are muscle tremors, muscle rigidity up to immobility, slowed movements and an unstable posture. Pergolide is available in Germany under the trade name Parkotil and in Austria and Switzerland as Permax. In addition, there are various generics of the Parkinson’s drug. Since the active ingredient can cause many side effects, especially in combination therapy, the patient must be monitored by a physician before starting treatment and regularly during therapy (blood pressure monitoring, ECG, etc.).
Pharmacologic effect
Pergolide belongs to the group of dopamine agonists and binds very strongly to proteins present in the blood. Dopamine agonists dock with dopamine receptors and mimic their actions, causing the neurotransmitter to be released. Pergolide binds to the D2 receptors. Dopamine is responsible for controlling motor activity in the body. If a stimulus is to be transmitted from one nerve cell to another in the brain, the sending nerve causes dopamine to be released. The neurotransmitter immediately docks with the dopamine receptors of the receiving nerve. An electrical impulse is then triggered there, which is transmitted by the nerve. This restores the patient’s ability to walk, stand up, reach or perform other movements more freely. Pergolide-containing drugs are prescribed as monotherapeutic agents to patients with Parkinson’s disease in the early stages. Later, the drug is usually used in combination with the classic Parkinson’s drug levodopa and a decarboxylase inhibitor. This is to support the positive effect of pergolide – it inhibits tremor and rigidity of movement – on the D2 dopamine agonists. Since the drug does not affect the adrenaline and serotonin receptors, the risk of mental impairment from pergolide is very low. If it is used together with L-dopa and a carboxylase inhibitor, their doses can be slowly reduced. Levodopa also becomes more tolerable for the patient.
Medical use and application
Pergolide is available as tablets in doses of 0.05, 0.25, and 1 mg. Combination therapy is usually used only when the drug alone is not effective enough. As a monotherapeutic, it is only a second-line agent. The tablets are taken according to the doctor’s instructions and dosed gradually from the start of treatment to keep the risk of side effects as low as possible. Alternatively, the patient can take 0.05 mg of pergolide once a day for the first two days. During the next 12 days, he increases his daily dose by two or three additional 0.25 mg every three days. Subsequently, 0.25 mg of pergolide is added every three days until the correct daily dose is reached. Beginning on the third day of dosing, daily doses are divided into several individual doses. In combination therapy, the daily L-dopa intake amount is reduced in parallel. Pergolide is taken unchewed before, with, or after a meal.
Risks and side effects
Pergolide should never be prescribed during pregnancy or while breastfeeding. In breastfeeding women, the drug inhibits the production of prolactin in the pituitary gland. In addition, the substance and its degradation products may eventually pass into breast milk.Young mothers should therefore either stop breastfeeding or discontinue the drug. If the patient is dependent on pergolide, she should refrain from becoming pregnant for the entire duration of treatment. Pergolide should never be used if the patient suffers from severe renal and hepatic insufficiency, severe cardiac arrhythmias, and other serious cardiac conditions such as pericardial effusion and myocarditis. In addition, the drug should not be prescribed to children and adolescents under any circumstances. Those who absolutely must take it should exercise special caution in traffic, as it can sometimes cause them to suddenly fall asleep. In case of chest pain and shortness of breath, it is advisable to consult a doctor immediately. Since pergolide is usually taken together with levodopa and a carboxylase inhibitor, the side effects cannot be precisely distinguished from one another. Patients may experience impaired movement (dyskinesia), nausea, vomiting, sleep disturbances, diarrhea, constipation, low blood pressure, poor appetite, rapid heartbeat, cardiac arrhythmias, kidney and liver dysfunction, rhinitis, shortness of breath, double vision, and short-term elevation of liver enzymes. Fibrotic altered heart valves have been found in more than one in five Parkinson’s patients. In rarer cases, pergolide may cause hallucinations and confusion. Taking dopamine agonists such as pergolide may potentiate or attenuate other concomitant medications.
