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Neurology Aug 2015
Topics: Antiparkinson Agents; Female; Humans; Male; Parkinson Disease; Placebo Effect
PubMed: 26304681
DOI: 10.1212/WNL.0000000000001879 -
The Consultant Pharmacist : the Journal... Apr 2018Five new drugs marketed within the last year, which are used for medical problems often experienced by the elderly, have been selected for consideration in this review....
Five new drugs marketed within the last year, which are used for medical problems often experienced by the elderly, have been selected for consideration in this review. The uses and most important properties of these agents are discussed, and a rating for each new drug is determined using the New Drug Comparison Rating system developed by the author (DAH). Advantages, disadvantages, and other important information regarding each new drug are identified and used as the basis for determining the rating. The drugs include an anticoagulant, an antiparkinson agent, an agent for tardive dyskinesia, an agent for psoriasis, and an agent for constipation. The drugs reviewed are betrixaban, safinamide mesylate, valbenazine tosylate, guselkumab, and plecanatide.
Topics: Aged; Alanine; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticoagulants; Antiparkinson Agents; Benzamides; Benzylamines; Constipation; Drug Approval; Humans; Natriuretic Peptides; Psoriasis; Pyridines; Tardive Dyskinesia; Tetrabenazine; Valine
PubMed: 29609697
DOI: 10.4140/TCP.n.2018.188 -
CNS Drugs Aug 2018The development of an intervention to slow or halt disease progression remains the greatest unmet therapeutic need in Parkinson's disease. Given the number of failures... (Review)
Review
The development of an intervention to slow or halt disease progression remains the greatest unmet therapeutic need in Parkinson's disease. Given the number of failures of various novel interventions in disease-modifying clinical trials in combination with the ever-increasing costs and lengthy processes for drug development, attention is being turned to utilizing existing compounds approved for other indications as novel treatments in Parkinson's disease. Advances in rational and systemic drug repurposing have identified a number of drugs with potential benefits for Parkinson's disease pathology and offer a potentially quicker route to drug discovery. Here, we review the safety and potential efficacy of the most promising candidates repurposed as potential disease-modifying treatments for Parkinson's disease in the advanced stages of clinical testing.
Topics: Animals; Antiparkinson Agents; Disease Progression; Drug Discovery; Drug Repositioning; Humans; Parkinson Disease
PubMed: 30066310
DOI: 10.1007/s40263-018-0548-y -
Drugs Feb 2022There has been exponential growth in the awareness and understanding of gastrointestinal (GI) dysfunction in Parkinson's disease (PD) over the past 3 decades. The... (Review)
Review
There has been exponential growth in the awareness and understanding of gastrointestinal (GI) dysfunction in Parkinson's disease (PD) over the past 3 decades. The clinical features of GI dysfunction in PD have been clearly identified and innovative research has demonstrated the presence of pathology within the enteric nervous system (ENS) in individuals with PD, leading to suggestions that the GI system may be ground zero for the genesis and the portal of entry of PD pathology, which then ascends via the vagus nerve to the central nervous system (CNS). This theory, as well as the more recent recognition of the association of PD with dysbiosis within the gut microbiota, has been the object of intense study and scrutiny. Since most PD medications are absorbed through the GI system, the need for better understanding of changes within the GI tract that may potentially affect the pattern of response to medications has become evident. In this review, current knowledge of the pathophysiology of changes within the GI tract and the gut microbiome of individuals with PD, including changes that occur with progression of the disease, will be addressed. We focus on common clinical GI problems in PD that can arise from different segments of the GI tract. Relevant diagnostic evaluations and treatment options for each of these problems will be reviewed.
Topics: Antiparkinson Agents; Deglutition Disorders; Diet; Enteric Nervous System; Gastrointestinal Diseases; Gastrointestinal Microbiome; Gastrointestinal Motility; Gastrointestinal Transit; Humans; Oral Health; Parkinson Disease; Weight Loss
PubMed: 35076890
DOI: 10.1007/s40265-021-01664-1 -
Clinics in Geriatric Medicine Feb 2020This article reviews the most common gastrointestinal (GI) problems that occur in patients with Parkinson disease, including weight loss, drooling, dysphagia, delayed... (Review)
Review
This article reviews the most common gastrointestinal (GI) problems that occur in patients with Parkinson disease, including weight loss, drooling, dysphagia, delayed gastric emptying, constipation, and defecatory dysfunction. Appropriate workup and treatment options are reviewed in detail in order to provide clinicians with a comprehensive and practical guide to managing these problems in Parkinson disease patients. GI adverse effects of commonly used Parkinson disease motor medications are also reviewed.
Topics: Aged; Antiparkinson Agents; Gastrointestinal Diseases; Humans; Parkinson Disease; Patient Care Management
PubMed: 31733704
DOI: 10.1016/j.cger.2019.09.003 -
Handbook of Experimental Pharmacology 2018Parkinson's disease (PD) is a progressive neurodegenerative disorder that compromises multiple neurochemical substrates including dopamine, norepinephrine, serotonin,... (Review)
Review
Parkinson's disease (PD) is a progressive neurodegenerative disorder that compromises multiple neurochemical substrates including dopamine, norepinephrine, serotonin, acetylcholine, and glutamate systems. Loss of these transmitter systems initiates a cascade of neurological deficits beginning with motor function and ending with dementia. Current therapies primarily address the motor symptoms of the disease via dopamine replacement therapy. Exogenous dopamine replacement brings about additional challenges since after years of treatment it almost invariably gives rise to dyskinesia as a side effect. Therefore there is a clear unmet clinical need for improved PD therapeutics. Opioid receptors and their respective peptides are expressed throughout the basal ganglia and cortex where monoaminergic denervation strongly contributes to PD pathology. Delta opioid receptors are of particular interest because of their dense localization in basal ganglia and because activating this system is known to enhance locomotor activity under a variety of conditions. This chapter will outline much of the work that has demonstrated the effectiveness of delta opioid receptor activation in models of PD and its neuroprotective properties. It also discusses some of the challenges that must be addressed before moving delta opioid receptor agonists into a clinical setting.
Topics: Animals; Antiparkinson Agents; Dyskinesia, Drug-Induced; Humans; Parkinson Disease; Receptors, Opioid, delta
PubMed: 27718057
DOI: 10.1007/164_2016_16 -
Current Pharmaceutical Design 2012Parkinson's disease (PD) is an age-associated neurodegenerative disease clinically characterized as a movement disorder. The motor symptoms in PD arise due to selective... (Review)
Review
Parkinson's disease (PD) is an age-associated neurodegenerative disease clinically characterized as a movement disorder. The motor symptoms in PD arise due to selective degeneration of dopaminergic neurons in the substantia nigra of the ventral midbrain thereby depleting the dopamine levels in the striatum. Most of the current pharmacotherapeutic approaches in PD are aimed at replenishing the striatal dopamine. Although these drugs provide symptomatic relief during early PD, many patients develop motor complications with long-term treatment. Further, PD medications do not effectively tackle tremor, postural instability and cognitive deficits. Most importantly, most of these drugs do not exhibit neuroprotective effects in patients. Consequently, novel therapies involving natural antioxidants and plant products/molecules with neuroprotective properties are being exploited for adjunctive therapy. Curcumin is a polyphenol and an active component of turmeric (Curcuma longa), a dietary spice used in Indian cuisine and medicine. Curcumin exhibits antioxidant, anti-inflammatory and anti-cancer properties, crosses the blood-brain barrier and is neuroprotective in neurological disorders. Several studies in different experimental models of PD strongly support the clinical application of curcumin in PD. The current review explores the therapeutic potential of curcumin in PD.
Topics: Age Factors; Animals; Antiparkinson Agents; Corpus Striatum; Curcuma; Curcumin; Disease Models, Animal; Dopamine; Humans; Neurons; Neuroprotective Agents; Parkinson Disease
PubMed: 22211691
DOI: 10.2174/138161212798918995 -
Advances in Experimental Medicine and... 2020Parkinson's disease (PD) is a major cause of morbidity and mortality among older individuals. Several researchers have suggested that iron chelators which cross the... (Review)
Review
Parkinson's disease (PD) is a major cause of morbidity and mortality among older individuals. Several researchers have suggested that iron chelators which cross the blood-brain barrier (BBB) might have clinical efficacy in treating PD. Therefore, efforts are made not only in order to improve the effect of L-dopa but also to introduce drugs which provide anti-parkinsonian and neuroprotective effects. In this study, quercetin, a flavonoid, exhibited noticeable neuroprotective effects via iron induced-oxidative stress-dependent apoptotic pathways. Our results suggested that quercetin significantly decreased the catalepsy and exhibited neuroprotective effects in rotenone-induced Parkinson. A model of rotenone-induced Parkinsonism in rats produced the decrease in glutathione, SOD, catalase, and serum iron concentration and the increase in H2O2 and lipid peroxidation activity. Quercetin efficiently halted the deleterious toxic effects of L-dopa, revealing normalization of catalepsy and rotarod score, in addition to amelioration of neurochemical parameters, indicating benefit of both symptomatic and neuroprotective therapies. In silico molecular docking studies have also shown that quercetin could be an ideal potential drug target for aromatic L-amino acid decarboxylase and human catechol-O-methyltransferase. In conclusion, quercetin possesses strong iron-chelating abilities and could be recommended as a disease-modifying therapy when administered in combination with L-dopa, early on in the course of Parkinson's disease.
Topics: Animals; Antiparkinson Agents; Aromatic-L-Amino-Acid Decarboxylases; Catechol O-Methyltransferase; Humans; Levodopa; Molecular Docking Simulation; Parkinson Disease; Quercetin
PubMed: 32468451
DOI: 10.1007/978-3-030-32633-3_1 -
Pharmacology & Therapeutics May 2023With L-DOPA, dopamine agonists such as pramipexole, ropinirole and rotigotine constitute key therapeutic options for the management of motor symptoms of Parkinson's... (Review)
Review
With L-DOPA, dopamine agonists such as pramipexole, ropinirole and rotigotine constitute key therapeutic options for the management of motor symptoms of Parkinson's disease. These compounds exert their beneficial effect on motor behaviours by activating dopamine D-class receptors and thereby compensating for the declining dopaminergic transmission in the dorsal striatum. Despite a strong similarity in their mechanism of action, these three dopamine agonists present distinct clinical profiles, putatively underpinned by differences in their pharmacological properties. In this context, this review aims at contributing to close the gap between clinical observations and data from molecular neuropharmacology by exploring the properties of pramipexole, ropinirole and rotigotine from both the clinical and molecular perspectives. Indeed, this review first summarizes and compares the clinical features of these three dopamine agonists, and then explores their binding profiles at the different dopamine receptor subtypes. Moreover, the signalling profiles of pramipexole, ropinirole and rotigotine at the D receptor are recapitulated, with a focus on biased signalling and the potential therapeutic implications. Overall, this review aims at providing a unifying framework of interpretation for both clinicians and fundamental pharmacologists interested in a deep understanding of the pharmacological properties of pramipexole, ropinirole and rotigotine.
Topics: Humans; Pramipexole; Dopamine Agonists; Dopamine; Receptors, Dopamine; Antiparkinson Agents
PubMed: 36958527
DOI: 10.1016/j.pharmthera.2023.108392 -
IDrugs : the Investigational Drugs... Jun 2007MitoQ is an orally active antioxidant that has the ability to target mitochondrial dysfunction. The agent is currently under development by Antipodean Pharmaceuticals... (Review)
Review
MitoQ is an orally active antioxidant that has the ability to target mitochondrial dysfunction. The agent is currently under development by Antipodean Pharmaceuticals Inc in phase II clinical trials for Parkinson's disease and liver damage associated with HCV infection. MitoQ has demonstrated encouraging preclinical results in numerous studies in isolated mitochondria, cells and tissues undergoing oxidative stress and apoptotic death. MitoQ aims to not only mimic the role of the endogenous mitochondrial antioxidant coenzyme Q10 (CoQ10), but also to augment substantially the antioxidant capacity of CoQ to supraphysiological levels in a mitochondrial membrane potential-dependent manner. MitoQ represents the first foray into the clinic in an attempt to deliver an antioxidant to an intracellular region that is responsible for the formation of increased levels of potentially deleterious reactive oxygen species. Results from the clinical trials with MitoQ will have important repercussions on the relevance of a mitochondrial-targeted approach.
Topics: Alzheimer Disease; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Antiparkinson Agents; Apoptosis; Clinical Trials as Topic; Friedreich Ataxia; Hepatitis C; Humans; Mitochondria; Myocardial Reperfusion Injury; Neuroprotective Agents; Organophosphorus Compounds; Oxidative Stress; Parkinson Disease; Ubiquinone
PubMed: 17642004
DOI: No ID Found