Apomorphine in the treatment of Parkinson's disease: a review

Pessoa, Renata Ramina; Moro, Adriana; Munhoz, Renato P.; Teive, Hélio Afonso Ghizoni; Lees, Andrew J.

doi:10.1590/0004-282x20180140

Cited by 36 publications

(25 citation statements)

References 58 publications

(195 reference statements)

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“…Once patients are able to tolerate it, they can inhale it up to five times per day as needed and expect a reversal of parkinsonian symptoms within 10-30 min. The time of onset is comparable to dissolvable benserazide:levodopa formulation 87 but slower than subcutaneous or sublingual apomorphine (7-10 min) 88 (table 1).…”

Section: Symptomatic Treatment Of Motor Symptoms Levodopamentioning

confidence: 95%

“…Apomorphine, a nonergoline dopamine agonist, is water soluble and lipophilic and is therefore suitable for intravenous, subcutaneous, sublingual, intranasal or transdermal administration. 88 . Apomorphine, when administered via subcutaneous injection, may provide a rapid rescue from hypomobility end-of-dose wearing off or unpredictable on/off episodes, typically observed in advanced PD.…”

Section: Dopamine Agonistsmentioning

confidence: 99%

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Parkinson’s disease: etiopathogenesis and treatment

Jankovic

Tan

2020

J Neurol Neurosurg Psychiatry

619

398

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The concept of ‘idiopathic’ Parkinson’s disease (PD) as a single entity has been challenged with the identification of several clinical subtypes, pathogenic genes and putative causative environmental agents. In addition to classic motor symptoms, non-motor manifestations (such as rapid eye movement sleep disorder, anosmia, constipation and depression) appear at prodromic/premotor stage and evolve, along with cognitive impairment and dysautonomia, as the disease progresses, often dominating the advanced stages of the disease. The key molecular pathogenic mechanisms include α-synuclein misfolding and aggregation, mitochondrial dysfunction, impairment of protein clearance (associated with deficient ubiquitin-proteasome and autophagy-lysosomal systems), neuroinflammation and oxidative stress. The involvement of dopaminergic as well as noradrenergic, glutamatergic, serotonergic and adenosine pathways provide insights into the rich and variable clinical phenomenology associated with PD and the possibility of alternative therapeutic approaches beyond traditional dopamine replacement therapies.One of the biggest challenges in the development of potential neuroprotective therapies has been the lack of reliable and sensitive biomarkers of progression. Immunotherapies such as the use of vaccination or monoclonal antibodies directed against aggregated, toxic α-synuclein.as well as anti-aggregation or protein clearance strategies are currently investigated in clinical trials. The application of glucagon-like peptide one receptor agonists, specific PD gene target agents (such as GBA or LRRK2 modifiers) and other potential disease modifying drugs provide cautious optimism that more effective therapies are on the horizon. Emerging therapies, such as new symptomatic drugs, innovative drug delivery systems and novel surgical interventions give hope to patients with PD about their future outcomes and prognosis.

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Section: Symptomatic Treatment Of Motor Symptoms Levodopamentioning

confidence: 95%

Section: Dopamine Agonistsmentioning

confidence: 99%

Parkinson’s disease: etiopathogenesis and treatment

Jankovic

Tan

2020

J Neurol Neurosurg Psychiatry

619

398

View full text Add to dashboard Cite

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“…Apomorphine is used primarily as a dopamine receptor agonist for the treatment of Parkinson's disease (Pessoa et al, 2018). The anti‐inflammatory effects of dopamine are mediated, at least in part, via β‐adrenoceptors (Hasko et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

High‐content screening identifies inhibitors of oxidative stress‐induced parthanatos: cytoprotective and anti‐inflammatory effects of ciclopirox

Regdon

Demény

Kovács

et al. 2021

British J Pharmacology

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Background and Purpose Excessive oxidative stress can induce PARP1‐mediated programmed necrotic cell death, termed parthanatos. Inhibition of parthanatos may be therapeutically beneficial in a wide array of diseases associated with tissue injury and inflammation. Our goal was to identify novel molecules inhibiting parthanatos. Experimental Approach A small library of 774 pharmacologically active compounds was screened in a Sytox Green uptake assay, which identified 20 hits that reduced hydrogen‐peroxide‐induced parthanatos with an efficiency comparable to the benchmark PARP inhibitor, PJ34. Key Results Of these hits, two compounds, antifungal ciclopirox and dopamine receptor agonist apomorphine, inhibited PAR polymer synthesis. These two compounds prevented the binding of PARP1 to oxidatively damaged DNA but did not directly interfere with the interaction between DNA and PARP1. Both compounds inhibited mitochondrial superoxide and H2O2 production and suppressed DNA breakage. Since H2O2‐induced damage is dependent on Fe2+‐catalysed hydroxyl radical production (Fenton chemistry), we determined the iron chelation activity of the two test compounds and found that ciclopirox and, to a lesser extent, apomorphine act as iron chelators. We also show that the Fe2+ chelation and indirect PARP inhibitory effects of ciclopirox translate to anti‐inflammatory actions as demonstrated in a mouse dermatitis model, where ciclopirox reduced ear swelling, inflammatory cell recruitment and poly(ADP‐ribosyl)ation. Conclusion and Implications Our findings indicate that the antimycotic drug, ciclopirox, acts as an iron chelator and thus targets an early event in hydrogen‐peroxide‐induced parthanatos. Ciclopirox has the potential to be repurposed as a cytoprotective and anti‐inflammatory agent.

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“…Since the oral bioavailability is 100%, apomorphine should be administered parenterally. For patients with PD who have refractory major "off" period, apomorphine is injected subcutaneously with an optimal dose ranging 3-5 mg and then provides the clinical effect at 5-15 min after administration (Pessoa et al 2018). Due to the short half-life (approximately 45 min), apomorphine can be injected with a 60min interval minimally.…”

Section: Apomorphinementioning

confidence: 99%

Course and Duration of Therapy with Parkinsonian Drugs and Withdrawal Syndromes

Aoyama

2019

NeuroPsychopharmacotherapy

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Current strategies for the treatment of Parkinson's disease (PD) are still mainly based on the use of dopaminergic medications such as L-dihydroxyphenylalanine (L-DOPA) and dopamine agonists to stimulate striatal dopamine receptors. Indeed, therapeutic intervention with these drugs has improved the prognosis of patients with PD over the last 50 years. However, it is still inconclusive as to which medication is the best for the initial treatment of PD and whether these medications have disease-modifying effects in the long clinical course of PD. In addition, long-term treatment with these drugs can cause complications that induce motor and non-motor symptoms, including withdrawal syndrome, in patients with PD. These symptoms are refractory to L-DOPA therapy and dominate the late-stage disability, which features some clinical milestones to the end of the disease. It is important to consider the influences of parkinsonian drug treatments on the clinical course of PD. In this chapter, therapy with parkinsonian drugs and their pharmacological properties, including adverse effects and influence on disease progression, will be discussed in detail.

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Apomorphine in the treatment of Parkinson's disease: a review

Cited by 36 publications

References 58 publications

Parkinson’s disease: etiopathogenesis and treatment

Parkinson’s disease: etiopathogenesis and treatment

High‐content screening identifies inhibitors of oxidative stress‐induced parthanatos: cytoprotective and anti‐inflammatory effects of ciclopirox

Course and Duration of Therapy with Parkinsonian Drugs and Withdrawal Syndromes

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