Dopamine Receptor Agonists
Dopamine receptor agonists are a class of drugs with similar actions to dopamine, a neurotransmitter that occurs naturally in the brain. A neurotransmitter is a chemical that allows the movement of information from one nerve cell (neuron) across the gap between the adjacent neuron. Dopaminergic receptors are protein complexes on the surface of certain neurons of the sympathetic autonomic nervous system that bind to dopamine.
Dopamine stimulates the heart, increases the blood flow to the liver, spleen, kidneys, and other visceral organs, and controls muscle movements and motor coordination through an inhibitory action over stimuli response. Abnormal low levels of dopamine are associated with
L-dopa (levodopa) is a precursor of dopamine, i.e., is converted into dopamine by the body. Levodopa thus increases dopamine levels in the motor areas of the central nervous system (CNS), especially in the initial stages of the disease. However, as the disease progresses, the drug loses its efficacy (effectiveness). When administered with carbidopa, levodopa's effects are enhanced because carbidopa increases L-dopa transport to the brain and decreases its gastrointestinal metabolism. Therefore, two beneficial effects are achieved: better results with lower doses of levodopa (4–5 times lower doses than in L-dopa therapy alone); and reduction or prevention of levodopa side effects, such as nausea, anorexia, vomiting, rapid heart rate, low blood pressure, mood changes, anxiety, and depression.
Bromocriptine mesylate is a derivative of ergotamine that inhibits the production of prolactin hormone by the pituitary gland. It is used in association with levodopa, in order to allow lower doses of the latter, especially in long-term therapy. Bromocriptine is also used to treat some menstrual disorders and infertility. This drug shows poor results in patients who do not respond to levodopa.
Pergolide mesylate has an action similar to that of bromocriptine, also inhibiting prolactin secretion. Also used in Parkinson's in association with L-dopa and carbidopa, pergolide is eliminated from the body through the kidneys. Cabergoline also inhibits prolactin secretion and is used to decrease abnormally high levels of this hormone, whether due to endocrine dysfunction or due to an existing pituitary tumor. The drug is also prescribed to regulate the menstrual cycle in cases of polycystic ovaries, and to control symptoms in Parkinson's disease.
Pramipexole and ropinirole are dopaminergic agonists that show good results in controlling Parkinson's symptoms in patients still in the initial stages of the disease and not yet treated with L-dopa, thus postponing the need of levodopa administration to a later phase. They work as well in those patients with advanced Parkinson's symptoms already taking levodopa.
Levodopa may worsen psychotic symptoms when administered to psychiatric patients and anti-psychotic drugs should not be taken with this medication. L-dopa is also contraindicated to patients with glaucoma, because it increases pressure within the eye. Patients with cardiac disorders must be carefully monitored during levodopa administration due to the risk of altered heart rhythms.
Bromocriptine is contraindicated (not advised) for children under 15 years old, in pregnancy, severe cardiac disease, and severely decreased kidney or liver function. Alcoholic beverages are contraindicated during bromocriptine use as well as the administration of diuretics or anti-psychotic drugs. Psychiatric disorders may worsen with the administration of this drug.
Pergolide is contraindicated in women who are breast-feeding or those with preexisting movement disorders or a psychotic condition. Patients with heart rhythm disturbances should be not take this medication.
Cabergoline is not indicated in cases of severe or uncontrolled hypertension (high blood pressure) or for women who are breast-feeding, and requires careful monitoring in patients with significant kidney or liver dysfunction. Pregnant women who are at risk for eclampsia should not take this medication as well.
Pramipexole and ropinirole are eliminated through the kidneys, and the simultaneous use of medications that decrease kidney function (such as cimetidine) requires medical monitoring. Patients with reduced kidney function also require careful follow up and dosage adjustments.
Bromocriptine may cause gastrointestinal discomfort, constipation, abdominal cramps, fatigue, anxiety, urinary incontinence or retention, depression, insomnia, hypotension, anorexia (loss of appetite), and rapid heart rate.
Pergolide side effects include dizziness when rising, increased heart rate, hallucinations, mood and personality disorders, ataxia (loss of coordination), muscle rigidity, blurred vision, anorexia, diarrhea, depression, insomnia, headache, confusion, numbness, gastritis, fluid retention, and swelling of the hands, face, and feet.
Cabergoline side effects include gastrointestinal irritation, gases, abdominal pain, digestive difficulties, dry mouth, loss of appetite, depression, mood changes, anxiety, insomnia, depression, increased sex drive, low blood pressure, fatigue, body weight changes.
Both pramipexole and ropinirole may cause hallucination (especially in elderly patients), dizziness and low blood pressure when rising, nausea, and gastrointestinal discomfort such as nausea and constipation. Pramipexole may also cause general swelling, fever, anorexia, and difficulty swallowing, decreased sex drive, amnesia and mental confusion, as well as insomnia and vision abnormalities. Ropinirole sometimes causes dizziness and fainting, with or without a slow heart rate.
Pyridoxine (vitamin B6) interferes with the transport of levodopa to the central nervous system by increasing its metabolism in the gastrointestinal tract. Dopamine antagonists (i.e., inhibitors of dopamine), such as metoclopramide and phenothiazines interfere with levodopa and other dopaminergic agonists, thus decreasing its effectiveness. The simultaneous concomitant use of phenelzine and dopamine agonists may induce severe high blood pressure.
Champe, Pamela C., and Richard A. Harvey, eds. Pharmacology, 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2000.
Weiner, William J., M.D. Parkinson's Disease: A Complete Guide for Patients and Families. Baltimore: Johns Hopkins University Press, 2001.
"Dopamine Agonists." WE MOVE. <http://www.wemove.org/par/par_dopa.html> (April 23, 2004).
"Pergolide." Medline Plus. National Library of Medicine. <http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a601093.html> (April 23, 2004).
National Parkinson Foundation. 1501 N.W. 9th Avenue, Bob Hope Research Center, Miami, Fl 33136-1494. (305) 243-6666 or (800) 327-4545; Fax: (305) 243-5595. firstname.lastname@example.org. <http://www.parkinson.org/>.