Dopamine agonists are a class of drugs that interact with dopamine receptors even when dopamine is absent. Dopamine agonists are chemical agents that bind to dopamine receptors and activate cell singulation pathways. Dopamine receptors are classified into two families based on their pharmacological, biochemical and genetic properties: the D1 dopamine receptor family includes D1 and D5 receptors, while the D2 dopamine receptor family includes D2, D3 and D4 receptors. All dopamine receptors couple to G proteins. The D1 and D5 receptors couple to the Gs family of G proteins, and thus an agonist that binds to these receptors activates adenylyl cyclase, thereby stimulating cAMP synthesis. D2, D3 and D4 receptors couple to the Gi/O family of G proteins, and agonists inhibit the synthesis of adenylyl cyclase and thus cAMP. High intracellular cAMP activates protein kinase A, which phosphorylates many downstream protein targets, including dopamine-32 kDa and cAMP-regulated phosphoprotein (DARPP-32), ionotropic glutamate receptor and GABA receptors. Since DARPP-32 inhibits protein phosphatase 1, this phosphoprotein regulates the phosphorylation state and thus the activity of various protein kinase A target proteins and neuronal activity. [12] Dopamine agonist drugs are divided into two classes of drugs – ergolines and non-ergoline. Prolactin production is usually triggered by an absence of dopamine, so low doses of dopamine agonists such as cabergoline and bromocriptine can be used to suppress prolactin production.
Although there is now clear evidence that dopamine agonists offer significant benefits in the treatment of Parkinson`s disease, both as monotherapy and when used with levodopa, most studies on dopamine agonists have been relatively short-term. However, the results of a recently completed 5-year study of the dopaminergic agonist ropinirole continue to support the results of previous studies on efficacy, safety and tolerability.21 Further long-term studies are needed to fully evaluate the efficacy and potential of dopamine agonists as monotherapy and neuroprotective agents. How dopamine agonists ultimately fit into Parkinson`s treatment strategies ultimately depends on the results of these long-term studies. With the exception of a recent study comparing long-term differences between bromocriptine and ropinirole,18 there was also a lack of studies sufficiently designed to determine whether there were significant differences in efficacy and tolerability between ergot and non-ergot dopamine agonists. The central dopaminergic agonistic properties of the semi-synthetic derivatives of ergoline lergotril, pergolide, bromocriptine and lisuride were detected. Some studies suggest that ergot alkaloids have the properties of mixed antagonists with respect to some presynaptic and postsynaptic receptors. N-n-propyl groups (chemical formula: –CH2CH2CH3) often enhance the effect of dopamine agonists in ergoline derivatives. Results from a 5-year randomized, double-blind trial comparing ropinirole with levodopa plus benzerazide in the treatment of 268 patients with early Parkinson`s disease were recently presented.21 Forty-seven percent of patients with ropinirole and 51% of patients with levodopa completed the 5-year study; Of these, 34% of patients on ropinirole received monotherapy. A lower dose of levodopa was required in patients receiving ropinirole than in patients receiving levodopa alone (427 mg/day versus 753 mg/day).
Similar clinical efficacy of treatment in the ropinirole and levodopa groups was demonstrated throughout the study (assessed by modifying the ADL score). Ropinirole monotherapy was also found to be associated with a significantly lower incidence of dyskinesia than levodopa monotherapy (5% vs. 36%; p<0.0001). In order to treat the ropinirole arm of the study (including patients saved from levodopa), the incidence of dyskinesia was still significantly reduced (20% for ropinirole versus 46% for levodopa; p<0.001). Typical side effects of dopaminergic agents caused 27% of patients on ropinirole and 29% of patients on levodopa to discontinue the study prematurely (not significantly different). Dopamine agonists are divided into two subgroups or classes of drugs, the first generation and newer drugs. Ergoline-derived agonists are the first generation and are not used as often as the new generation of non-ergonomic agonists. Ergoline-derived agonists are considered "dirtier" drugs because of their interaction with receptors other than dopamine receptors, so they cause more side effects. Ergoline-derived agonists are, for example, bromocriptine, cabergoline, pergolide, and lisuride. Non-ergolinic agonists are pramipexole, ropinirole, rotigotine, piribedil and apomorphine. [1] Dopamine agonists are synthetic drugs that stimulate dopamine receptors.
They are often used to treat Parkinson`s disease and in lower doses for restless legs syndrome. This class of drugs includes pramipexole (Mirapex), ropinirole (Requip) and rotigotine transdermal patch (Neupro). These drugs have special properties with unique side effects that are not intuitively associated with the drug. Therefore, a short chapter is devoted to these side effects. If the patient is not taking any of these medications, this chapter can be skipped. A few years ago, clinicians realized that pramipexole and ropinirole were associated with the development of pathological gambling. Even insidiously, a minority of people who were prescribed these drugs began to feel the desire to gamble, as in casinos or online. For some, it was an exacerbation of previous trends, but for others, this desire came out of nowhere, with no history of gambling. Other types of compulsive pathological behaviors were quickly recognized in some people treated with these drugs. These included inappropriate hypersexual behaviours (extramarital affairs, pornography) and compulsive spending, eating, drinking or smoking.
For many people, this behavior was completely atypical. The common element was the initiation of pramipexole or ropinirole. The behaviors did not develop immediately, but became insidiously evident after the drug slowly degenerated into the therapeutic range. Patients and family were often unaware of the behavior or relationship with the drug until they were specifically asked about it at the doctor`s office. The common theme of these compulsive behaviors is that they inherently reward the human experience. It has been recognized that the use of these dopamine agonists by some people is associated with a pathological urge to engage excessively in activities such as gambling, sex, diet or spending. For those affected, it began to dominate their thoughts and actions. Who would think that a drug could promote certain hedonistic or rewarding behaviors? However, clinical experience and published evidence support this risk. The two main active ingredients that have been linked are pramipexole (Mirapex) and ropinirole (Requip).
The rotigotine patch has also been linked to such behaviors, but apparently less common. Depressive symptoms and disorders are common in patients with Parkinson`s disease and can affect their quality of life. [8] Increased anxiety can increase the symptoms of Parkinson`s disease and is therefore essential to treat. Instead of conventional antidepressants in the treatment of depression, treatment with dopamine agonists has been suggested. [9] Dopamine agonists are primarily thought to help treat symptoms and depressive disorders by relieving motor complications, which are one of the main symptoms of Parkinson`s disease. Although preliminary evidence for clinical trials has shown interesting results, further research is crucial to determine the antidepressant effects of dopamine agonists in the treatment of symptoms and depressive disorders in patients with Parkinson`s disease. [8] The increase often occurs with dopamine agonists and related drugs such as L-DOPA. When dopamine agonists are used for a long period of time or at higher doses, the risk of increased increases. Impulse control disorder, which is described as gambling, hypersexuality, compulsive shopping, and binge eating, is a serious side effect of dopamine agonists. [14] Dopamine agonists can be used as first-line treatment for symptoms of Parkinson`s disease at an early stage and in younger people. In later stages of the disease, combinations of L-DOPA, dopamine agonists and other drugs may be used.
They can occur with any Parkinson`s medication, but are more common with dopamine agonists. Not everyone will experience this side effect and it is more common in the later stages of Parkinson`s disease. To avoid an increase with long-term treatment, lower doses of dopamine agonists and iron substitutes (if serum ferritin levels are below 70) are recommended. If an increase occurs, the drug may need to be stopped, but it can be successfully reintroduced later. Contraindications to dopamine agonists are pregnancy and nursing mothers, since these drugs inhibit lactation. Nausea, vomiting, orthostatic hypotension, headache, dizziness and cardiac arrhythmias are the most common side effects of dopamine agonists. [13] These side effects are primarily dose-dependent. It is strongly recommended to start these drugs at low doses to reduce the risk of orthostatic hypotension. Antiemetics antagonistic to serotonin receptors should not be taken together, as they can enhance the hypotensive effect of dopamine agonists.