Audio LecturePro Feature Dopamine Agonists 0:00 / 0:00 1x 0.25x 0.5x 0.75x 1x 1.25x 1.5x 1.75x 2x Dopamine agonists are an important group of medicines used to manage the motor symptoms of Parkinson’s disease. This article covers the indications, mechanisms of action, pharmacokinetics, contraindications, cautions, adverse effects and clinically important drug interactions of commonly used dopamine agonists. It also covers amantadine, an antiparkinsonian medicine with a different mechanism of action that can be used to reduce levodopa-induced dyskinesia. Indications for Use Dopamine agonists are used in the treatment of motor symptoms in Parkinson’s disease. Common non-ergot dopamine agonists include: Pramipexole Ropinirole Rotigotine All of the above are also licensed for the symptomatic treatment of moderate-to-severe restless legs syndrome. Ergot-derived dopamine agonists include bromocriptine, cabergoline and pergolide, which are not used as first line options due to their association with fibrotic complications and cardiac valvulopathy. Bromocriptine inhibits the release of prolactin, therefore can also be used to suppress lactation, in hypogonadism, prolactinoma and infertility. Apomorphine is also a potent dopamine agonist available as a continuous subcutaneous infusion or as bolus injections, used for the management of advanced Parkinson’s disease, particularly when patients experience disabling motor fluctuations despite optimised oral treatment. Mechanism of Action Dopamine Agonists Dopamine agonists bind and activate dopamine receptors in the striatum. Bromocriptine and cabergoline, pramipexole and ropinirole are selective for D2/3 receptors. Rotigotine is active at the D3, D2 and D1 receptors of the caudate-putamen in the brain. Apomorphine is selective for D1 and D2 receptors. Amantadine Amantadine has a different mechanism from dopamine agonists. Its antiparkinsonian effects are thought to involve several mechanisms, including: NMDA receptor antagonism enhancement of dopaminergic transmission increased dopamine release reduced dopamine reuptake some anticholinergic activity. Amantadine is also effective in reducing dyskinesias. Created in BioRender. Boucher, M. (2026) https://BioRender.com/lo7nlpg Fig 1Drugs Against Parkinson’s Disease – Mechanism of Action Pharmacokinetics The following table describes key pharmacokinetic parameters for dopamine agonists and amantadine used in Parkinson’s disease. Drug Absorption Distribution Metabolism Excretion Pramipexole Dopamine agonist F >90%. Tmax = 1-3 hours. Food does not affect the extent of absorption but slows the rate. Very low plasma protein binding (<20%). Large volume of distribution (~400 L). High concentrations occur in brain tissue. Minimally metabolised. 90% renal elimination – dose adjustment required in renal impairment T ½ = 12 hours Ropinirole Dopamine agonist F~ 50%. TMax~1.5 hours. A high-fat meal delays absorption and reduces Cmax by ~25%. Large volume of distribution (~7 L/kg). highly lipophilic. Low plasma protein binding 10-40%. Primarily metabolised by CYP1A2. Major metabolites have substantially less dopaminergic activity than ropinirole. Metabolites are mainly excreted in urine. T ½ = 6 hours. Bromocriptine Ergot dopamine agonist Tmax = 1–3 hours. Extensive first-pass metabolism occurs. ~96% plasma protein bound. Extensively metabolised by CYP3A4 Parent drug and metabolites are almost completely eliminated via the liver; only approximately 6% is eliminated renally. T ½ ~15 hours. Apomorphine Dopamine agonist – subcutaneous Effects begin within approximately 4-12 minutes. Two-compartment distribution. Distribution half-life approximately 5 minutes. Clinical response correlates with CSF concentrations. Metabolised by glucuronidation and sulphonation. T ½ 33 minutes, accounting for its short duration of action of around 1 hour. Rotigotine Dopamine agonist – transdermal Steady-state concentrations are reached after 1-2 days. Absolute bioavailability ~37%. Food does not affect absorption. Approximately 92% protein bound. Very large apparent volume of distribution (~84 L/kg). Extensively metabolised by N-dealkylation and conjugation. Several CYP isoforms can contribute. Main metabolites are biologically inactive. 71% excreted renally and 23% in faeces. T ½ 5-7 hours Amantadine Other antiparkinsonian drug Almost completely absorbed orally, Tmax = 3-4 hours. Crosses the blood-brain barrier. 67% protein bound, Large volume of distribution (5–10 L/kg). Minimally metabolised 90% excreted renally. T ½ ~15 hours, may be considerably prolonged in older people and renal impairment. Contraindications Contraindications to dopamine agonists differ between different drugs and are described below. All drugs are contraindicated in patients with a hypersensitivity to the drug or excipients. Amantadine Amantadine is contraindicated in patients with a history of gastric ulceration, severe renal impairment, pregnancy and patients prone to convulsions. Ropinirole Ropinirole is contraindicated in severe renal impairment (CrCl <30ml/min) and hepatic impairment Rotigotine MRI or cardioversion due to the aluminium backing layer on the patch which can lead to burns during these procedures. Apomorphine Apomorphine has several contraindications including respiratory depression, dementia, psychotic disease and hepatic insufficiency. Furthermore if patients experience an “on” response to levodopa complicated by severe dyskinesia or dystonia, treatment with apomorphine is not recommended. Apomorphine is also contraindicated alongside ondansetron which is described in further detail under “interactions”. Bromocriptine Bromocriptine is contraindicated in uncontrolled hypertension including in pre-eclampsia. Furthermore in coronary artery disease, severe cardiovascular disease and serious psychiatric disorders. There have been rare serious cases of hypertension, myocardial infarction, stroke and psychiatric disorders in postpartum women treated with bromocriptine to inhibit lactation. Adverse Effects and Cautions Nausea and Vomiting Nausea and vomiting are side effects of nearly all drugs that increase dopamine release in the brain, as dopaminergic neurons play a vital role in nausea and vomiting. Dopamine receptors, particularly D2 receptors in the chemoreceptor trigger zone, contribute to the emetic response. Antiemetics which work as dopamine antagonists in the chemoreceptor trigger zone, such as domperidone, may be an effective treatment option to treat nausea in some patients with Parkinson’s disease because there is limited penetration of the blood-brain barrier. Domperidone does not act on dopamine receptors in the basal ganglia therefore is not expected to worsen Parkinson’s symptoms or antagonise the effects of dopamine agonists for Parkinson’s. Patients treated with subcutaneous apomorphine usually need to start domperidone at least 2 days before starting therapy and caution using apomorphine is advised for patients who are prone to nausea and vomiting. However, domperidone is associated with QT prolongation and cardiac adverse effects, which needs to be considered before prescribing. Metoclopramide, another antiemetic which antagonises dopamine receptors, does act in the basal ganglia therefore is contraindicated in Parkinson’s disease. It is recommended that ropinirole is taken with food to mitigate gastrointestinal side effects. Cardiac Dopamingeric drugs can also cause hypotension therefore should be used with caution in cardiovascular disease. Furthermore apomorphine can cause QT prolongation therefore should be used with caution in patients at risk of torsades de pointes and alongside other drugs which can cause QT prolongation. With long term use, ergot-derived dopamine agonists like cabergoline, bromocriptine and pergolide have risk of cardiac fibrosis. Long term and high dose treatment with bromocriptine can lead to further fibrotic complications such as pulmonary and retroperitoneal fibrosis. Neurological Dopaminergic drugs can also cause psychological effects such as schizophrenia-like syndrome, confusion, disorientation, insomnia, sudden onset of sleep or nightmares, therefore should be used with caution in cognitive or psychiatric disease and in the elderly. Impulse control disorders can occur with dopaminergic drugs such as levodopa, pramipexole and ropinirole. This can be displayed as gambling, overeating, compulsive buying and sexual excess. Axial dystonia can occur with pramipexole which is characterised by involuntary muscle contractions affecting the trunk, neck and sometimes the face. Withdrawal Abrupt withdrawal of dopaminergic agents including amantadine can cause neuroleptic malignant-like syndrome which may include symptoms such as muscular rigidity, hyperpyrexia and psychological changes. Furthermore, dopamine agonist withdrawal syndrome may occur which involves anxiety, depression, fatigue, sweating and pain. Gradual tapering should occur if therapy is to be stopped, and it is vital patients get their medications on time. Amantadine Amantadine has a different adverse effect profile, some of which result from its anticholinergic effects, important adverse effects include: livedo reticularis peripheral oedema lowering of the seizure threshold confusion hallucinations dizziness insomnia nightmares dry mouth urinary retention Interactions Dopamine Antagonists Dopamine antagonists such as antipsychotics may worsen Parkinson’s symptoms via antagonism of dopaminergic drugs, therefore concomitant administration should only be undertaken with caution. Pramipexole Inhibitors and competitors of the active renal elimination pathway such as cimetidine, amantadine, quinine and procainamide may increase pramipexole levels via reduced renal clearance. Ropinirole Ropinirole is metabolised by CYP1A2 therefore increased levels may occur when administered alongside CYP1A2 inhibitors such as ciprofloxacin or fluvoxamine. Smoking induces CYP1A2 therefore this may lead to subtherapeutic levels of ropinirole. Bromocriptine Bromocriptine is metabolised by CYP3A4 therefore inhibitors such as macrolides and azole antifungals may increase bromocriptine levels and thus adverse effects. Bromocriptine is also an inhibitor of CYP3A4, however low therapeutic concentrations of free bromocriptine mean that significant interactions with CYP3A4 substrates are not expected. Apomorphine Caution should be applied with dopamine agonists and drugs that can cause hypotension due to the risk of an additive effect. Specifically, apomorphine is contraindicated alongside ondansetron and other 5-HT3 antagonists due to risk of profound hypotension and loss of consciousness. Amantadine Amantadine has an anticholinergic effect, so concomitant use with other anticholinergic drugs can increase anticholinergic adverse effects such as confusion, dry mouth and urinary retention. Concomitant administration with trimethoprim may increase amantadine levels, as both medicines compete for renal secretion. References Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan DJ. Rang & Dale’s Pharmacology. 9th ed. London: Elsevier; 2019. Hitchings BSc, M., Lonsdale, D., Burrage, D., Baker, E. (2022). The Top 100 Drugs – E-Book. Netherlands: Elsevier. MIRAPEXIN 0.18 mg tablets – Summary of Product Characteristics (SmPC) – (emc) | 7694 Accessed 24/8/26 Requip 0.25 mg Film-coated Tablets – Summary of Product Characteristics (SmPC) – (emc) | 1160 Accessed 24/8/26 Bromocriptine 2.5mg Tablets – Summary of Product Characteristics (SmPC) – (emc) | 1202 Acccessed 21/09/26 Scenario: Confirmed Parkinson’s disease | Management | Parkinson’s disease | CKS | NICE Accessed 21/09/26 APO-go PFS 5mg/ml Solution for Infusion in Pre-filled Syringe – Summary of Product Characteristics (SmPC) – (emc) | 3908 Accessed 25/09/26 Neupro 4 mg/24 h transdermal patch – Summary of Product Characteristics (SmPC) – (emc) | 1996 Accessed 25/09/26 Amantadine Hydrochloride 100 mg Hard Capsules – Summary of Product Characteristics (SmPC) – (emc) | 15613 Accessed 25/09/26 Amantadine – UKCPA Handbook of Perioperative Medicines Accessed 5/10/26 Do you think you’re ready? Take the quiz below QuizPro Feature Dopamine Agonists Question 1 of 3 Submitting... Skip Next Rate question: You scored 0% Skipped: 0/3 More Questions Available Upgrade to TeachMePharmacy Pro Challenge yourself with over 400 multiple-choice questions to reinforce learning. Learn More Frequent questions What are dopamine agonists used for in Parkinson’s disease? Dopamine agonists are used to improve motor symptoms in Parkinson’s disease by activating dopamine receptors in the striatum. Common non-ergot agents include pramipexole, ropinirole and rotigotine, while apomorphine is used for advanced disease with disabling motor fluctuations. How do dopamine agonists work? Dopamine agonists directly stimulate dopamine receptors in the striatum, mainly D2 and D3 receptors. Rotigotine acts at D1, D2 and D3 receptors, whereas apomorphine acts at D1 and D2 receptors. What is apomorphine used for and how is it administered? Apomorphine is used in advanced Parkinson’s disease when disabling motor fluctuations persist despite optimised oral treatment. It is given by subcutaneous infusion or bolus injection, with effects beginning after approximately 4–12 minutes and lasting around one hour. What are the important adverse effects of dopamine agonists? Important adverse effects include nausea, vomiting, hypotension, psychological disturbances, sudden sleep onset and impulse control disorders. Ergot-derived agents can cause cardiac fibrosis, while apomorphine may prolong the QT interval. Why should dopamine agonists not be stopped suddenly? Dopaminergic medicines should be withdrawn gradually because abrupt cessation can cause a neuroleptic malignant-like syndrome or dopamine agonist withdrawal syndrome. Possible features include muscular rigidity, high temperature, psychological changes, anxiety, depression, fatigue, sweating and pain. Rate This Article