Motor Complications of Chronic Levodopa Therapy in Parkinsonʼs Disease

Miyawaki, Edison; Lyons, Kelly; Pahwa, Rajesh; Tröster, Alexander I.; Hubble, Jean; Smith, Diane; Busenbark, Karen; McGuire, D.; Michalek, Debra; Koller, William C.

doi:10.1097/00002826-199712000-00004

Cited by 72 publications

(28 citation statements)

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“…Although the dopamine replacement using levodopa (L-dopa) is the mainstay of pharmacologic treatments for PD, this drug becomes less effective due to increased incidence of nonmotor symptoms or adverse events in later stages of PD (430,518), and often worsens bladder overactivity in mild-to-advanced patients due to activation of dopamine D2-receptors (84,650). However, preclinical and clinical studies of adenosine A 2A receptor antagonists have provided promising results for motor dysfunction in PD patients (508,552) which prompted an examination of the effect of an adenosine A 2A receptor antagonist on the micturition reflex in a rat model of PD (330).…”

Section: Agingmentioning

confidence: 99%

Neural Control of the Lower Urinary Tract

1997

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This article summarizes anatomical, neurophysiological, pharmacological, and brain imaging studies in humans and animals that have provided insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract. The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain, spinal cord, and peripheral autonomic ganglia that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet. The neural control of micturition is organized as a hierarchical system in which spinal storage mechanisms are in turn regulated by circuitry in the rostral brain stem that initiates reflex voiding. Input from the forebrain triggers voluntary voiding by modulating the brain stem circuitry. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic reflex pathway that has essential connections in the periaqueductal gray and pontine micturition center. A computer model of this circuit that mimics the switching functions of the bladder and urethra at the onset of micturition is described. Micturition occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary micturition, leading to urinary incontinence. Neuroplasticity underlying these developmental and pathological changes in voiding function is discussed.

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Section: Agingmentioning

confidence: 99%

Neural Control of the Lower Urinary Tract

1997

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“…After about 5 years of continuous treatment with L-dopa, at least half of PD patients develop fluctuating motor responses, and nearly three quarters do so by 15 years [126]. These fluctuations (so-called "on-off" effects) include "off" periods of immobility, and "on" periods with abnormal involuntary movements or dyskinesias (Fig.…”

Section: Dopaminergic Pharmacotherapymentioning

confidence: 99%

“…They can greatly complicate clinical management of PD patients, including those with clinical depression commonly associated with PD, or dementia that sometimes arises in late stages of the disease. Modern antidepressants usually are well tolerated, with inconsistent and probably minor risk of worsening bradykinesia with serotonin-enhancing antidepressants [126]. Use of antipsychotic drugs, however, is limited to those with minimal risk of worsening bradykinesia and other aspects of extrapyramidal motor dysfunction [127,128].…”

Section: Dopaminergic Pharmacotherapymentioning

confidence: 99%

“…These reactions include hallucinations, delusions, and confusion, suggesting delirium, and are most likely in elderly PD patients with symptoms of dementia. Treatment is similar to psychotic reactions encountered during Ldopa therapy, and usually includes use of low doses of such antipsychotic agents as clozapine or quetiapine [126,173,192]. Adverse peripheral and central dopaminergic effects, including nausea, hypotension, and agitation also occur with ropinirole and pramipexole.…”

Section: Drugs Targeting Dopamine Receptorsmentioning

confidence: 99%

“…Synthetic central anticholinergic agents include benztropine mesylate (51), biperiden (52), the antihistamine diphenhydramine (53), the phenothiazine ethopropazine (54), orphenadrine (55), procyclidine (56), and trihexylphenidyl (57). Such drugs continue to be used to control parkinsonism and other adverse extrapyramidal neurological effects of potent D 2 -receptor antagonist antipsychotic agents, for which they are quite effective [17,126].…”

Section: Agents Acting On Nondopaminergic Systemsmentioning

confidence: 99%

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Therapeutic and Diagnostic Agents for Parkinson's Disease

Booth

Neumeyer

Baldessarini

2010

Burger's Medicinal Chemistry and Drug Discovery

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This chapter summarizes the neurobiology of Parkinson's disease and medicinal chemistry relevant to treatment of this neurodegenerative disorder with neuropsychiatric complications. The chapter also surveys basic clinical features of Parkinson's disease, its neuropathophysiology and etiology. Considered are genetic, maturational, metabolic, and environmental contributors to risk for the disease. Pharmacotherapy for Parkinson's disease includes l ‐dopa to counter cerebral dopamine deficiency, direct dopaminergic agonists, and agents that prolong the actions of l ‐dopa or dopamine by preventing their metabolism by peripheral aromatic amino acid decarboxylase, catechol‐ O ‐methyltransferase, or monoamine oxidase. Additional drugs acting on nondopaminergic systems include muscarinic acetylcholine, adenosine, and l ‐glutamate antagonists, as well as serotonin (5‐hydroxytryptamine) agonists. Agents used to diagnose Parkinson's disease and monitor its progression, include radioactive compounds used to image brain l ‐dopa and dopamine neurotransporters and dopamine receptors. Finally, potential contributions are considered of medicinal chemistry to improve pharmacotherapy of Parkinson's disease.

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Evaluation of Dyskinesias in a Pilot, Randomized, Placebo-Controlled Trial of Remacemide in Advanced Parkinson Disease

2001

Arch Neurol

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Motor Complications of Chronic Levodopa Therapy in Parkinsonʼs Disease

Cited by 72 publications

References 0 publications

Neural Control of the Lower Urinary Tract

Neural Control of the Lower Urinary Tract

Therapeutic and Diagnostic Agents for Parkinson's Disease

Evaluation of Dyskinesias in a Pilot, Randomized, Placebo-Controlled Trial of Remacemide in Advanced Parkinson Disease

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