Utilization of COMT inhibitors, dopamine agonists, and MAO-B inhibitors with levodopa-carbidopa instestinal gel in advanced Parkinson's disease patients: Summary of phase 3 and real-world studies

2019 ◽  
Vol 405 ◽  
pp. 29-30
Author(s):  
K.R. Chaudhuri ◽  
J. Boyd ◽  
J. Acosta ◽  
L. Bergmann ◽  
P. Kukreja ◽  
...  
Author(s):  
M. Luke James ◽  
Ulrike Hoffmann

This chapter on Parkinson’s disease discusses the epidemiology and clinical features of the disease. It also covers the pathophysiology and clinically relevant staging, as well as peri-operative considerations for the anaesthetist, including the effects of surgery and anaesthesia on various organ systems of the patient with Parkinson’s disease. The chapter also covers a range of appropriate drug treatments, including dopamine, dopamine agonists, monoamine oxidase-B inhibitors (MAO-B inhibitors), anticholinergic agents, NMDA antagonists, and catechol-O-methyl-transferase inhibitors (COMT inhibitors). Lastly, it discusses the treatment of Parkinson-associated depression, fatigue, dementia and psychosis, neuroleptic malignant syndrome (NMS), anaesthesia management, and implantation of deep brain stimulators.


2020 ◽  
Vol 76 (12) ◽  
pp. 1731-1743
Author(s):  
Caroline D. Binde ◽  
Ingunn F. Tvete ◽  
Jørund I. Gåsemyr ◽  
Bent Natvig ◽  
Marianne Klemp

Abstract Purpose To investigate the comparative effectiveness of dopamine agonists and monoamine oxidase type-B (MAO-B) inhibitors available for treatment of Parkinson’s disease. Methods We performed a systematic literature search identifying randomized controlled trials investigating 4 dopamine agonists (cabergoline, pramipexole, ropinirole, rotigotine) and 3 MAO-B inhibitors (selegiline, rasagiline, safinamide) for Parkinson’s disease. We extracted and pooled data from included clinical trials in a joint model allowing both direct and indirect comparison of the seven drugs. We considered dopamine agonists and MAO-B inhibitors given as monotherapy or in combination with levodopa. Selected endpoints were change in the Unified Parkinson’s Disease Rating Scale (UPDRS) score, serious adverse events and withdrawals. We estimated the relative effectiveness of each dopamine agonist and MAO-B inhibitor versus comparator drug. Results Altogether, 79 publications were included in the analysis. We found all the investigated drugs to be effective compared with placebo when given as monotherapy except safinamide. When considering combination treatment, the estimated relative effects of selegiline, pramipexole, ropinirole, rotigotine, cabergoline, rasagiline and safinamide were 2.316 (1.819, 2.951), 2.091 (1.889, 2.317), 2.037 (1.804, 2.294), 1.912 (1.716, 2.129), 1.664 (1.113, 2.418), 1.584 (1.379, 1.820) and 1.179 (1.031, 1.352), respectively, compared with joint placebo and levodopa treatment. Conclusions Dopamine agonists were found to be effective as treatment for Parkinson’s disease, both when given as monotherapy and in combination with levodopa. Selegiline and rasagiline were also found to be effective for treating Parkinson’s disease, and selegiline was the best option in combination with levodopa among all the drugs investigated.


2019 ◽  
Vol 19 (2) ◽  
pp. 133-145 ◽  
Author(s):  
Idalet Engelbrecht ◽  
Jacobus P. Petzer ◽  
Anél Petzer

Background: The most effective symptomatic treatment of Parkinson’s disease remains the metabolic precursor of dopamine, L-dopa. To enhance the efficacy of L-dopa, it is often combined with inhibitors of the enzymes, catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) B, key metabolic enzymes of L-dopa and dopamine. Objective: This study attempted to discover compounds that exhibit dual inhibition of COMT and MAO-B among a library of 40 structurally diverse natural compounds. Such dual acting inhibitors may be effective as adjuncts to L-dopa and offer enhanced value in the management of Parkinson’s disease. Methods: Selected natural compounds were evaluated as in vitro inhibitors of rat liver COMT and recombinant human MAO. Reversibility of MAO inhibition was investigated by dialysis. Results: Among the natural compounds morin (IC50 = 1.32 µM), chlorogenic acid (IC50 = 6.17 µM), (+)-catechin (IC50 = 0.86 µM), alizarin (IC50 = 0.88 µM), fisetin (IC50 = 5.78 µM) and rutin (IC50 = 25.3 µM) exhibited COMT inhibition. Among these active COMT inhibitors only morin (IC50 = 16.2 µM), alizarin (IC50 = 8.16 µM) and fisetin (IC50 = 7.33 µM) were noteworthy MAO inhibitors, with specificity for MAO-A. Conclusion: None of the natural products investigated here are dual COMT/MAO-B inhibitors. However, good potency COMT inhibitors have been identified, which may serve as leads for future development of COMT inhibitors.


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