Neuroprotective Role of Dopamine Agonists

Herrero, M.T.; Pagonabarraga, Javier; Linazasoro, Gurutz

doi:10.1097/nrl.0b013e31823968fc

Cited by 19 publications

(5 citation statements)

References 129 publications

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“…The ELLDOPA trial in 2004 [91] refuted these findings, and the American Academy of Neurology (AAN) guidelines in 2006 used this evidence to state that L-dopa did not accelerate disease progression [92]. There was vigorous debate in the field at this time on the benefits of commencing therapy with DA agonists to delay onset of L-dopa-induced dyskinesia (LID) and other potential benefits of reduced development of LID we anticipated might have altered prescribing but this was only evident in marginal trends [93, 94]. Recently, the LEAP study revealed that L-dopa has no disease-modifying effects [95]; however, the high reliance on L-dopa could be explained by its higher efficacy and better safety profile than other PD medications [96, 97].…”

Section: Discussionmentioning

confidence: 99%

Patterns and Determinants of Prescribing for Parkinson’s Disease: A Systematic Literature Review

Orayj

Lane

2019

Parkinson's Disease

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Since the discovery of levodopa (L-dopa) in 1967, the range of medications available to treat Parkinson's disease has increased significantly and guidance on the use, efficacy, and safety of these medications has evolved. To assess levels of adherence to national prescribing guidelines and awareness of changes in the efficacy and safety data published in the profiles of medications for the treatment of PD, we have reviewed studies on patterns and determinants of prescribing PD medications conducted in the last 50 years (since the discovery of L-dopa). A systematic literature review was conducted using EMBASE (1967 to March, 2018), Ovid MEDLINE(R) ALL (1967 to March 16, 2018), PsycINFO (1967 to the 2nd week of March, 2018), and PubMed to identify all studies measuring prescribing patterns of PD medication between 1967 and 2017. Study design, source of data, country, year of study, number of patients and/or prescriptions, unit of analysis, prescribing determinants, and percentage utilisation of PD medications were extracted where possible. 44 studies examining prescribing patterns and/or prescribing determinants across 17 countries were identified. Unsurprisingly, L-dopa was the most commonly prescribed medication in all studies, accounting for 46.50% to 100% of all prescriptions for PD. In several studies, the prescribing rate of ergot-derived dopamine agonists (DAs) decreased over time in concordance with guidance. In contrast, the prescribing rates of non-ergot DAs increased over the last ten years in most of the included studies. In examining prescribing factors, two major categories were exemplified, patients' factors and prescribers' factors, with patients' age being the most common factor that affected the prescription in most studies. In conclusion, L-dopa is now the most commonly prescribed medication for cases of PD but there is large variation in the prescribing rates of catechol-O-methyltransferase (COMT) inhibitors, monoamine oxidase B (MAO-B) inhibitors, amantadine, and anticholinergics between countries. New studies examining the effects of recent clinical trials and measuring the prescribing rates of newly approved medications are warranted.

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Section: Discussionmentioning

confidence: 99%

Patterns and Determinants of Prescribing for Parkinson’s Disease: A Systematic Literature Review

Orayj

Lane

2019

Parkinson's Disease

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“…Continued disagreement regarding the toxicity of levodopa likely contributed to the observed delay in response. The notion that DAs are less toxic (rather than simply less potent) continues to have a strong footing in the scientific literature and lay press [ 31 , 32 ]. Notwithstanding any disagreement, recent evidence reaffirms the AAN’s finding that levodopa is not toxic [ 10 , 33 – 35 ].…”

Section: Discussionmentioning

confidence: 99%

Trends in inpatient antiparkinson drug use in the USA, 2001–2012

Crispo

Fortin

Thibault

et al. 2015

Eur J Clin Pharmacol

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PurposeAlthough therapeutic options and clinical guidelines for Parkinson’s disease (PD) have changed significantly in the past 15 years, prescribing trends in the USA remain unknown. The purpose of this population-based cohort study was to examine patterns of inpatient antiparkinson drug use between January 2001 and December 2012 in relation to clinical guideline publication, drug introduction/withdrawal, and emerging safety concerns.MethodsA total of 16,785 inpatients receiving pharmacological treatment for PD were identified in the Cerner Health Facts database. Our primary outcome was standardized (age, sex, race, and census region) annual prevalence of antiparkinson drug use. We also examined antiparkinson medication trends and polypharmacy by age and sex.ResultsThe most frequently prescribed antiparkinson drugs between 2001 and 2012 were levodopa (85 %) and dopamine agonists (28 %). Dopamine agonist use began declining in 2007, from 34 to 27 % in 2012. The decline followed publication of the American Academy of Neurology’s practice parameter refuting levodopa toxicity, pergolide withdrawal, and pramipexole label revisions. Despite safety concerns for cognitive impairment and falls, individuals ≥80 years of age demonstrated stable rates of dopamine agonist use from 2001 to 2012. Polypharmacy was most common in younger patients.ConclusionsDopamine agonist use declined from 2007 to 2012, suggesting that increased awareness of safety issues and practice guidelines influenced prescribing. These events appear to have minimally influenced treatment provided to older PD patients. Antiparkinson prescribing trends indicate that safety and best practice information may be communicated effectively.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-015-1881-4) contains supplementary material, which is available to authorized users.

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“…While L-dopa is still the pharmacological gold standard for PD, among other symptomatic treatments for motor symptoms of PD, DA receptor agonists had been found to be promising, although their use in the clinic is still nondefinitive. Among neuroprotective strategies to limit the PD progression, D2 DA receptor agonists are often a part of pharmacological therapy for early PD 24 – 26 and could protect neurons of both the nucleus striatum and the substantia nigra by a variety of actions including the modulation of mitochondrial function. Thus, neuroprotection of cortico- and nigrostriatal circuits is a direct consequence of the restorative dopaminergic strategies.…”

Section: Introductionmentioning

confidence: 99%

Dopamine D2 receptor-mediated neuroprotection in a G2019S Lrrk2 genetic model of Parkinson’s disease

et al. 2018

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Parkinson’s disease (PD) is a neurodegenerative disorder in which genetic and environmental factors synergistically lead to loss of midbrain dopamine (DA) neurons. Mutation of leucine-rich repeated kinase2 (Lrrk2) genes is responsible for the majority of inherited familial cases of PD and can also be found in sporadic cases. The pathophysiological role of this kinase has to be fully understood yet. Hyperactivation of Lrrk2 kinase domain might represent a predisposing factor for both enhanced striatal glutamatergic release and mitochondrial vulnerability to environmental factors that are observed in PD. To investigate possible alterations of striatal susceptibility to mitochondrial dysfunction, we performed electrophysiological recordings from the nucleus striatum of a G2019S Lrrk2 mouse model of PD, as well as molecular and morphological analyses of G2019S Lrrk2-expressing SH-SY5Y neuroblastoma cells. In G2019S mice, we found reduced striatal DA levels, according to the hypothesis of alteration of dopaminergic transmission, and increased loss of field potential induced by the mitochondrial complex I inhibitor rotenone. This detrimental effect is reversed by the D2 DA receptor agonist quinpirole via the inhibition of the cAMP/PKA intracellular pathway. Analysis of mitochondrial functions in G2019S Lrrk2-expressing SH-SY5Y cells revealed strong rotenone-induced oxidative stress characterized by reduced Ca2+ buffering capability and ATP synthesis, production of reactive oxygen species, and increased mitochondrial fragmentation. Importantly, quinpirole was able to prevent all these changes. We suggest that the G2019S-Lrrk2 mutation is a predisposing factor for enhanced striatal susceptibility to mitochondrial dysfunction induced by exposure to mitochondrial environmental toxins and that the D2 receptor stimulation is neuroprotective on mitochondrial function, via the inhibition of cAMP/PKA intracellular pathway. We suggest new possible neuroprotective strategies for patients carrying this genetic alteration based on drugs specifically targeting Lrrk2 kinase domain and mitochondrial functionality.

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Neuroprotective Role of Dopamine Agonists

Cited by 19 publications

References 129 publications

Patterns and Determinants of Prescribing for Parkinson’s Disease: A Systematic Literature Review

Patterns and Determinants of Prescribing for Parkinson’s Disease: A Systematic Literature Review

Trends in inpatient antiparkinson drug use in the USA, 2001–2012

Dopamine D2 receptor-mediated neuroprotection in a G2019S Lrrk2 genetic model of Parkinson’s disease

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