Movement Disorder Drugs are pharmaceuticals used to treat neurological disorders known as movement disorders, which impair the body's capacity to regulate its movements and cause aberrant motor function.[1] These conditions can show up as either insufficient movement, as in Parkinson's disease, or excessive movement, like tremors or tics.[1] Huntington's disease, essential tremor, and dystonia are common forms of movement disorders, each with its own set of symptoms and underlying causes.[1] Several drug classes play crucial roles in the treatment of movement disorders, each targeting specific mechanisms to alleviate symptoms.
Many drug classes, including anticholinergics, benzodiazepines, beta blockers, dopaminergic agents, COMT inhibitors, and MAO-B inhibitors, and are essential for treating movement disorders.[1] Together, these drug classes form a comprehensive approach to manage the diverse challenges presented by movement disorders, improve patients' functional abilities and reduce symptoms. Optimising treatment and improving the quality of life for people with movement disorders requires an understanding of the pharmacological landscape of movement disorder medications.
Medical Use of Movement Disorder Drugs
editA class of pharmaceuticals known as movement disorder drugs is intended to treat a range of neurological disorders that impair the ability to control one's body's movements. By addressing neurotransmitter imbalances in the brain, these medications seek to reduce symptoms of movement disorders, including tremors and hypokinesia.[1] Common medications for movement disorders include anticholinergics, dopaminergics (such as levodopa), MAO-B inhibitors, and other pharmacological agents designed to treat particular conditions like essential tremor, dystonia, and Parkinson's disease.[2] These drugs improve motor function and the general quality of life for people with movement disorders by modifying neurotransmitter activity.[1]
Drug Classes
editAnticholinergics
edit
Mechanism of Action
editAnticholinergics are a group of medicines that block the action of acetylcholine, a neurotransmitter that controls muscles and thinking.[3]
Medical Uses
editThey are mainly used for movement disorders, especially Parkinson’s disease, where they help with symptoms like tremors and rigidity. By blocking acetylcholine at muscarinic receptors, anticholinergics rebalance acetylcholine and dopamine which is often disrupted in conditions like Parkinson’s disease.[4]
Drug Examples
editBenzatropine and trihexyphenidyl are commonly prescribed anticholinergics and are most effective in younger patients or those with milder symptoms.[4]
Side Effects
editDespite the benefits, anticholinergics are not without risks. They can cause a range of side effects including dry mouth, blurred vision, constipation and urinary retention. More worrying is the link to long term anticholinergic use and cognitive decline especially in older adults. Studies have shown that prolonged use of these drugs can increase the risk of dementia and other cognitive impairments and healthcare providers are cautious when prescribing them to elderly patients.[5] The concept of “anticholinergic burden” also highlights the cumulative effect of multiple medications with anticholinergic properties which can lead to serious outcomes like confusion and delirium.[5]
Conclusion for Anticholinergics
editOngoing research is crucial to understanding the long-term effects of anticholinergics and to optimize their use. Clinicians must make sure benefits are over risks to ensure safe and effective treatment strategies. Continued investigation will help elucidate the best practices for incorporating these medications into broader therapeutic regimens for movement disorders.
Benzodiazepines
edit
Mechanism of Action
editBenzodiazepines are a class of drugs used to treat anxiety, sedation, sleep, muscle relaxation and anticonvulsant effect. They work by increasing the action of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABA receptor which leads to increased neuronal inhibition and a calming effect on the central nervous system.[6]
Medical Uses
editBenzodiazepines can relieve muscle spasms associated with conditions like multiple sclerosis and are often used to manage alcohol withdrawal symptoms, helping to prevent complications such as seizures.[7]
Drug Examples
editCommon drug examples include lprazolam, chlordiazepoxide, clorazepate, diazepam, halazepam, lorzepam, oxazepam, prazepam, and quazepam.[8]
Side Effects
editCommon side effects include drowsiness, dizziness and reduced coordination which can be a major risk of falls especially in the elderly.[9] Studies have also shown that long term use of benzodiazepines may be linked to cognitive decline and increased risk of dementia. So it’s important for health care providers to carefully assess the appropriateness of benzodiazepine therapy, considering the patient’s medical history, potential for substance use disorders and presence of co-occurring mental health conditions.
Conclusion for Bezodiazepines
editThe use of benzodiazepines should be part of a comprehensive treatment plan that includes psychotherapy and other non-pharmacological interventions. Ongoing research is needed to understand the long term effects of benzodiazepines and to establish guidelines for prescription that prioritizes patient safety while managing anxiety and related disorders.[10]
Beta Blockers
editMechanism of Action
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Beta blockers, also known as beta receptor antagonists, are medications targeting beta receptors.[1] These receptors are involved in the sympathetic nervous system and located in the brain, heart, and smooth muscle.[1] Beta blockers can inhibit the the binding of noradrenaline and adrenaline to the beta receptors and hence reduce the activity of the receptors, resulting in decreased stimulation to the target tissue.[2] [11] Since sympathetic activity may result in skeletal muscle tremor, some β blockers, e.g. propranolol, are found effective for relieving tremor.[11] However, the mechanism of reliving tremor is still unclear.[2]
Pharmacokinetics
editThe duration of action of propranolol is around 6-12 hours for immediately release tablet or 24-27 hours for extended release formulation.[12] Since propranolol undergoes extensive first-pass metabolism, its bioavailability is low.[12]
Medical Uses
editExample of beta blockers include propranolol, metoprolol, atenolol, etc. Regarding the treatment of movement disorders, propranolol is found to be useful in the symptom control of essential tremor, which is a postural tremor sometimes caused by genetic factors or dysfunction of beta receptors.[13]
Contraindications
editBeta blockers are contraindicated in patients with decompensated heart failure, heart block, or asthma.[12]
Side Effects
editCommon side effects of propanolol include fatigue, depression, sexual dysfunction, and low heart rate.[3]
Dopaminergic Agents
editDopamine is a crucial neurotransmitter in the central nervous system that regulates various physiological processes, such as emotion, memory, motor activity, etc.[3] Dysregulation of dopamine is a significant cause for movement disorders, making dopaminergic agents essential for treatment. Therefore, dopaminergic agents are commonly used to manage movement disorders such as Parkinson’s disease and restless leg syndrome.[3] The primary classes of dopaminergic medications include levodopa and dopamine agonists. Both of them play vital roles in increasing dopaminergic stimulation and alleviating symptoms associated with these disorders.[11]
Levodopa
editMechanism of Action
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Levodopa, also known as L-Dopa, serves as a precursor to dopamine.[11] Once administered, levodopa is converted to dopamin by an enzyme, aromatic L-amino acid decarboxylase (AADC) in the central nervous system and the peripheral region.[14] The resulted dopamine will effectively stimulate the dopamine receptors.[11] To enhance its efficacy and minimize side effects, levodopa is typically combined with a decarboxylase inhibitor like carbidopa.[1] This combination prevents the premature conversion of levodopa into dopamine before reaching the brain.[11]
Medical Uses
editLevodopa is considered the first-line treatment for Parkinson’s disease.[15] It is also employed for the treatment of restless leg syndrome and dystonia.[1]
Contraindications
editLevodopa should be avoided in psychotic patients since it may worsen the mental status of the patients.[11] It is also contraindicated in patients with angle-closure glaucoma. Levodopa should be given with cautions in patients with active peptic ulcer because gastrointestinal bleeding occurs occasionally when taking levodopa.[11]
Interactions
editLevodopa has a significant interaction with monoamine oxidase A (MAO-A) inhibitors.[11] It should not be given to patients who are taking MAO-A inhibitors or have discontinued MAO-A inhibitors within 2 weeks, since this combination may result in hypertensive crises.[11]
Side Effects
editCommon side effects of levodopas include anorexia, nausea, vomiting, orthostatic hypotension, sudden sleep onset, drowsiness, agitation, hallucination and confusion.[16] The half-life of levodopa is short (around 1-2 hours).[17] This means the improvement of the motor symptoms will be gone in a short time, resulting in the fluctuation in the improvement of the symptoms. This phenomenon is called “wearing-off”[1] Moreover, long-term use may result in decreased effectiveness of levodopa and dyskinesias.[3]
Dopamine Agonists
editMechanism of Action
editDopamine agonists directly target D2 dopamine receptors.[3] By binding to these receptors, they can stimulate the dopamine receptors to mimic dopamine's effects.[3]
Medical Uses
editDopamin agonists are effective for managing Parkinson’s disease, restless leg syndorme, and dystonia. There are two categories of dopamine agonists, including ergot derivatives and non-ergot derivatives.[3] One of the ergot derivatives currently available is apomorphine. It is used as a rescue therapy for acute off episodes in patients with fluctuation in repose when using dopaminergic therapy.[15] Non-ergot derivatives, such as pramipexole, ropinirole, and rotigotine, are FDA-approved medications for the treatment of Parkinson’s disease and restless leg syndrome.[3]
Contraindications
editDopamine agonists are contraindicated in patients with psychotic disorders, myocardial infarction, or active peptic ulceration.[11] The ergot-derived agonists should be avoided when patients have peripheral vascular disease.[11]
Side Effects
editCommon side effects of dopamine agonists include hallucinations, confusion, nausea, and orthostatic hypotension.[3]
Catechol-O-Methyltransferase (COMT) Inhibitors
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Mechanism of Action
editCatechol-O-Methyltransferase (COMT) is an enzyme metabolizing catecholamines, e.g. dopamine, noradrenaline, etc.[11] Levodopa, as a catecholamine, is also a substrate of COMT. COMT can degrade levodopa to to 3-O-methylDOPA.[3] The COMT inhibitors can inhibit the COMT enzyme and block the degradation of levodopa before levodopa enters the brain.[3] This can increase the half-life of levodopa in the blood and hence more levodopa can enter the brain.[1] Moreover, COMT inhibitor targeting COMT in the central nervous system can also block the metabolism of dopamine.[3]
Pharmacokinetics
editRegarding the distribution of the drugs, entacapone cannot pass through the blood brain barrier, so it primarily acts on peripheral COMT.[5] Tolcapone can pass pass through the blood brain barrier, so it can inhibit both peripheral and central COMT.[5]
Medical Uses
editExamples of COMT inhibitors include tolcapone and entacapone. Since COMT inhibitors can promote the effect of levodopa, they are usually taken in combination with levodopa in the treatment of Parkinson’s disease.[15]
Contraindications
editTolcapone should be avoided in patient with abnormal liver function test results or liver diseases.[18]
Side Effects
editCommon side effects of COMT inhibitors include nausea, orthostatic hypotension, vivid dreams, confusion, and hallucinations.[3] Tolcapone may also cause toxicity in liver which may be fetal.[11]
Monoamine Oxidase-B Inhibitors
editMechanism of Action
editOne class of drugs called MAO-B inhibitors is mainly used to treat Parkinson's disease. These medications function by preventing monoamine oxidase type B (MAO-B), an enzyme that breaks down dopamine in the brain, from doing its job. MAO-B inhibitors improve dopamine availability by inhibiting this enzyme, which may lessen Parkinson's disease-related motor symptoms.[19]
Medical Uses
editIn order to increase the effectiveness of other treatments, like levodopa, and lessen motor fluctuations, MAO-B inhibitors can be used as monotherapy in the early stages of Parkinson's disease or as an adjuvant.[20] Although there is currently no conclusive proof of disease modification in humans, these drugs may also provide advantages of neural protection by lowering oxidative stress linked to dopamine metabolism.[19]
Drug Examples
editCurrently, selegiline, rasagiline, and safinamide are the three primary MAO-B inhibitors utilised in clinical practice.[20]
Pharmacokinetics
editSince selegiline and rasagiline are irreversible inhibitors, their effects last for a long time because they create a permanent bond with the MAO-B enzyme. On the other hand, because safinamide is a reversible inhibitor, enzyme activity can return more quickly after stopping the medication.[19]
Side Effects
editCommon side effects include various emotional disturbances and psychiatric problems, motor fluctuations, freezing episodes, and dyskinesia.[21]
Conclusion for MAO-B Inhibitors
editMAO inhibitors are effective antidepressants that enhance mood by inhibiting monoamine oxidase. They require dietary restrictions to avoid hypertensive reactions but can be beneficial for treatment-resistant depression.
References
edit- ^ a b c d e f g h i j k l Goldman, Jennifer G. (2022). Jankovic, Joseph; Hallett, Mark; Okun, Michael S.; Comella, Cynthia; Fahn, Stanley (eds.). Principles and practice of movement disorders (3rd ed.). London New York Oxford Philadelphia St Louis Sydney: Elsevier. ISBN 978-0-323-31071-0.
- ^ a b c Iansek, Robert; Morris, Meg E. (2013). Rehabilitation in Movement Disorders (1st ed.). Cambridge University Press. doi:10.1017/cbo9781139012942. ISBN 978-1-107-01400-8.
- ^ a b c d e f g h i j k l m n Brunton, Laurence; Knollmann, Björn C. (2022). Goodman & Gilman's the pharmacological basis of therapeutics (14th ed.). New York: McGraw Hill. ISBN 978-1-264-25808-6.
- ^ a b Vanegas-Arroyave, Nora; Caroff, Stanley N.; Citrome, Leslie; Crasta, Jovita; McIntyre, Roger S.; Meyer, Jonathan M.; Patel, Amita; Smith, J. Michael; Farahmand, Khody; Manahan, Rachel; Lundt, Leslie; Cicero, Samantha A. (2024). "An Evidence-Based Update on Anticholinergic Use for Drug-Induced Movement Disorders". CNS Drugs. 38 (4): 239–254. doi:10.1007/s40263-024-01078-z. ISSN 1172-7047. PMC 10980662. PMID 38502289.
- ^ a b c d Chepke, Craig; Vanegas-Arroyave, Nora; Cicero, Sam; Bron, Morgan (2023-03-01). "Use of Anticholinergics for Drug-Induced Movement Disorders With Implications for Elderly Patients". The American Journal of Geriatric Psychiatry. 31 (3): S125 – S126. doi:10.1016/j.jagp.2022.12.176. ISSN 1064-7481.
- ^ Edinoff, Amber N.; Nix, Catherine A.; Hollier, Janice; Sagrera, Caroline E.; Delacroix, Blake M.; Abubakar, Tunde; Cornett, Elyse M.; Kaye, Adam M.; Kaye, Alan D. (2021-11-10). "Benzodiazepines: Uses, Dangers, and Clinical Considerations". Neurology International. 13 (4): 594–607. doi:10.3390/neurolint13040059. ISSN 2035-8377. PMC 8629021. PMID 34842811.
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- ^ "List of Common Benzodiazepines + Uses & Side Effects". Drugs.com. Retrieved 2025-04-08.
- ^ Lader, Malcolm (2011-10-17). "Benzodiazepines revisited—will we ever learn?". Addiction. 106 (12): 2086–2109. doi:10.1111/j.1360-0443.2011.03563.x. ISSN 0965-2140.
- ^ Olfson, Mark; Blanco, Carlos; Wang, Shuai; Laje, Gonzalo; Correll, Christoph U. (2014-01-01). "National Trends in the Mental Health Care of Children, Adolescents, and Adults by Office-Based Physicians". JAMA Psychiatry. 71 (1): 81. doi:10.1001/jamapsychiatry.2013.3074. ISSN 2168-622X.
- ^ a b c d e f g h i j k l m n Katzung, Bertram G.; Trevor, Anthony J. (2020). Basic & Clinical Pharmacology. McGraw-Hill's AccessMedicine (15th ed.). New York, N.Y: McGraw-Hill Education LLC. ISBN 978-1-259-64115-2.
- ^ a b c UpToDate (2025-04-08). "Propranolol: Drug information". Lexi-Drugs, UpToDate Lexidrug. Retrieved 2025-04-08.
- ^ Ferreira, Joaquim J.; Mestre, Tiago A.; Lyons, Kelly E.; Benito‐León, Julián; Tan, Eng‐King; Abbruzzese, Giovanni; Hallett, Mark; Haubenberger, Dietrich; Elble, Rodger; Deuschl, Günther (2019-05-02). "MDS evidence‐based review of treatments for essential tremor". Movement Disorders. 34 (7): 950–958. doi:10.1002/mds.27700. ISSN 0885-3185.
- ^ Nutt, John G. (2008). "Pharmacokinetics and pharmacodynamics of levodopa". Movement Disorders. 23 (S3): S580 – S584. doi:10.1002/mds.22037. ISSN 0885-3185.
- ^ a b c Connolly, Barbara S.; Lang, Anthony E. (2014-04-23). "Pharmacological Treatment of Parkinson Disease". JAMA. 311 (16): 1670. doi:10.1001/jama.2014.3654. ISSN 0098-7484.
- ^ UpToDate (2025-04-08). "Carbidopa and levodopa: Drug information". Lexi-Drugs, UpToDate Lexidrug. Retrieved 2025-04-08.
- ^ LeWitt, Peter A. (2015). "Levodopa therapy for Parkinson's disease: Pharmacokinetics and pharmacodynamics". Movement Disorders. 30 (1): 64–72. doi:10.1002/mds.26082. ISSN 1531-8257.
- ^ UpToDate (2025-04-08). "Tolcapone: Drug information". Lexi-Drugs, UpToDate Lexidrug. Retrieved 2025-04-08.
- ^ a b c Nam, Min-Ho; Sa, Moonsun; Ju, Yeon Ha; Park, Mingu Gordon; Lee, C. Justin (2022-04-18). "Revisiting the Role of Astrocytic MAOB in Parkinson's Disease". International Journal of Molecular Sciences. 23 (8): 4453. doi:10.3390/ijms23084453. ISSN 1422-0067.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ a b "MAO-B inhibitors (rasagiline, selegiline, safinamide)". Parkinson's UK. Retrieved 2025-03-18.
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