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Parkinsonism & Related Disorders Oct 2023Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars... (Review)
Review
Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. Although the exact etiology of PD remains elusive, growing evidence suggests a complex interplay of genetic, environmental, and lifestyle factors in its development. Despite advances in pharmacological interventions, current treatments primarily focus on managing symptoms rather than altering the disease's underlying course. In recent years, natural phytocompounds have emerged as a promising avenue for PD management. Phytochemicals derived from plants, such as phenolic acids, flavones, phenols, flavonoids, polyphenols, saponins, terpenes, alkaloids, and amino acids, have been extensively studied for their potential neuroprotective effects. These bioactive compounds possess a wide range of therapeutic properties, including antioxidant, anti-inflammatory, anti-apoptotic, and anti-aggregation activities, which may counteract the neurodegenerative processes in PD. This comprehensive review delves into the pathophysiology of PD, with a specific focus on the roles of oxidative stress, mitochondrial dysfunction, and protein malfunction in disease pathogenesis. The review collates a wealth of evidence from preclinical studies and in vitro experiments, highlighting the potential of various phytochemicals in attenuating dopaminergic neuron degeneration, reducing α-synuclein aggregation, and modulating neuroinflammatory responses. Prominent among the natural compounds studied are curcumin, resveratrol, coenzyme Q10, and omega-3 fatty acids, which have demonstrated neuroprotective effects in experimental models of PD. Additionally, flavonoids like baicalein, luteolin, quercetin, and nobiletin, and alkaloids such as berberine and physostigmine, show promise in mitigating PD-associated pathologies. This review emphasizes the need for further research through controlled clinical trials to establish the safety and efficacy of these natural compounds in PD management. Although preclinical evidence is compelling, the translation of these findings into effective therapies for PD necessitates robust clinical investigation. Rigorous evaluation of pharmacokinetics, bioavailability, and potential drug interactions is imperative to pave the way for evidence-based treatment strategies. With the rising interest in natural alternatives and the potential for synergistic effects with conventional therapies, this review serves as a comprehensive resource for pharmaceutical industries, researchers, and clinicians seeking novel therapeutic approaches to combat PD. Harnessing the therapeutic potential of these natural phytocompounds may hold the key to improving the quality of life for PD patients and moving towards disease-modifying therapies in the future.
Topics: Humans; Parkinson Disease; Neuroprotective Agents; Quality of Life; Flavonoids; Dopaminergic Neurons; Alkaloids; Disease Management
PubMed: 37633805
DOI: 10.1016/j.parkreldis.2023.105799 -
Toxins Nov 2023In a few regions of the globe, deliberate botanical intoxication may induce significant rates of toxicity and fatality. The objective of this report was to describe... (Review)
Review
INTRODUCTION
In a few regions of the globe, deliberate botanical intoxication may induce significant rates of toxicity and fatality. The objective of this report was to describe plant self-intoxication using the experiences of the southeastern France poison control center (PCC) between 2002 and 2021.
RESULTS
During those 20 years, 262 deliberate plants poisonings were reported involving 35 various plants. In most of the cases, poisoning was caused by (n = 186, 71%), followed by the genus (4.2%), (3.8%), (1.9%), (1.2%), (1.9%), (1.5%), and (1.2%). Through the 262 plants poisonings, 19 patients among the 186 poisonings received Digifab as an antidote and 1 patient received physostigmine among the 11 Datura poisonings. Only four deaths were reported for this review, each involving .
DISCUSSION
The first involved species was (71% of all plants poisonings), then sp and . It is explained by this native local species' important repartition. Most patients must be admitted to an emergency department for adapted medical care; however, only 41 of them described severe poisonings symptoms. Even fewer needed an antidote, only 20 patients. There is no protocol for the use of a specific treatment, and it might be interesting to develop one for this purpose.
MATERIAL AND METHODS
This retrospective review was realized with files managed by the southeastern France PCC based in Marseille from 2002 to 2021. Our department covers the complete French Mediterranean coast, Corsica, and tropical islands (Reunion Island, Mayotte). For every patient, toxicity was evaluated using the Poison Severity Score (PSS).
Topics: Humans; Antidotes; France; Plant Poisoning; Poisons; Suicide, Attempted
PubMed: 38133175
DOI: 10.3390/toxins15120671 -
Clinical Toxicology (Philadelphia, Pa.) Feb 2024Anticholinergic agents are commonly taken in overdose, often causing delirium. The spectrum of anticholinergic delirium ranges from mild agitation to severe behavioural...
INTRODUCTION
Anticholinergic agents are commonly taken in overdose, often causing delirium. The spectrum of anticholinergic delirium ranges from mild agitation to severe behavioural disturbance. Physostigmine is an effective treatment for anticholinergic delirium, but its availability is limited. As rivastigmine is readily available, it has been used to manage anticholinergic delirium; however, there is limited research investigating its use.
METHOD
This was a retrospective review of patients with anticholinergic delirium treated in two toxicology units with rivastigmine (oral capsule or transdermal patch) from January 2019 to June 2023. The primary outcome was the use of further parenteral treatment (sedation or physostigmine) for delirium post rivastigmine administration.
RESULTS
Fifty patients were administered rivastigmine for the management of anticholinergic delirium. The median age was 36 years (interquartile range: 25-49 years) and 27 (54 per cent) were females. Features consistent with anticholinergic toxicity included tachycardia in 44 (88 per cent) and urinary retention requiring catheterisation in 40 (80 per cent). Forty-three patients (86 per cent) were treated with physostigmine before rivastigmine administration. Twenty-two were managed with transdermal rivastigmine (most commonly 9.5 mg/24 hour patch), and 28 with oral rivastigmine 6 mg. Further parenteral sedation and/or physostigmine treatment were required more often in patients given transdermal than oral rivastigmine [16/22 (73 per cent) versus 9/28 (32 per cent), = 0.010)]. No patients had bradycardia or gastrointestinal symptoms following rivastigmine administration. One patient with a history of epilepsy had a seizure, 1.5 hours post physostigmine administration and 7 hours post transdermal rivastigmine.
DISCUSSION
Rivastigmine has been increasingly used for the management of patients with anticholinergic delirium, due to the lack of availability of physostigmine. In this case series, rivastigmine transdermal patch appeared to be less effective than oral rivastigmine capsules, likely due to its slow onset of action and/or insufficient dose.
CONCLUSION
Rivastigmine can be used to treat anticholinergic delirium. In our case series oral rivastigmine appeared more effective than transdermal rivastigmine.
Topics: Female; Humans; Adult; Male; Rivastigmine; Physostigmine; Cholinergic Antagonists; Cholinesterase Inhibitors; Delirium
PubMed: 38465631
DOI: 10.1080/15563650.2024.2319854 -
Brain and Nerve = Shinkei Kenkyu No... Dec 2023Eserine, well-known as physostigmine, is classified as an alkaloid. It is a cholinesterase inhibitor and appears in Agatha Christie's novel entitled, Crooked House and...
Eserine, well-known as physostigmine, is classified as an alkaloid. It is a cholinesterase inhibitor and appears in Agatha Christie's novel entitled, Crooked House and Curtain: Poirot's Last Case. In clinical medicine, eserine was used as an ophthalmic treatment for glaucoma and considered as a treatment for myasthenia gravis, Alzheimer's disease, and hereditary cerebellar ataxias. Currently, it is used as a treatment for anticholinergic poisoning.
Topics: Humans; Physostigmine; Cholinesterase Inhibitors; Myasthenia Gravis
PubMed: 38097226
DOI: 10.11477/mf.1416202536 -
Journal of Medical Toxicology :... Jan 2024Physostigmine fell out of widespread use in the 1980s due to safety concerns; however, more recent research has demonstrated that its safety profile is better than...
INTRODUCTION
Physostigmine fell out of widespread use in the 1980s due to safety concerns; however, more recent research has demonstrated that its safety profile is better than previously thought. These studies have mainly included adults. We theorized that improved safety data may lead to more acceptance. Our objectives, therefore, were to characterize current frequency of use of physostigmine in pediatric patients as well as to study adverse effect rates in a national pediatric patient population.
METHODS
The National Poison Data System was queried for cases of patients aged 0-18 years that involved single-substance exposures to antimuscarinic xenobiotics that were reported to a poison center between January 1, 2000, and December 31, 2020. Cases were stratified into groups by therapy received: benzodiazepines alone, benzodiazepines and physostigmine, physostigmine alone, or no physostigmine or benzodiazepines. Patient demographics, clinical effects, and medical outcomes were analyzed.
RESULTS
A total of 694,132 cases were reviewed, and 150,075 were included for analysis. Nearly 5% (7562/150,075) of patients received specific pharmacological therapy with benzodiazepines, physostigmine, or both. A benzodiazepine as a single agent was the most frequently used pharmacologic therapy (92% of 7562). Among patients receiving any pharmacological therapy, only 8.3% (n = 627) of patients received physostigmine. Frequency of serious outcomes significantly increased across the study period among patients receiving benzodiazepines alone or with physostigmine. There was no increase in serious outcomes among patients receiving only physostigmine.
CONCLUSIONS
Physostigmine frequency of use was low overall, but when used, was associated with less severe outcomes when compared to benzodiazepines.
PubMed: 38265619
DOI: 10.1007/s13181-024-00988-0 -
The Journal of Emergency Medicine Oct 2023Anticholinergic toxicity is a common cause of delirium in emergency department patients. The standard antidotal treatment for anticholinergic toxicity is physostigmine....
BACKGROUND
Anticholinergic toxicity is a common cause of delirium in emergency department patients. The standard antidotal treatment for anticholinergic toxicity is physostigmine. Physostigmine functions as a reversible acetylcholinesterase inhibitor that readily crosses the blood-brain barrier. Rivastigmine is another member of this class currently approved for the treatment of Alzheimer's disease and Parkinson's disease. Rivastigmine also crosses the blood-brain barrier and has been found to be effective in the management of anticholinergic toxicity in limited case reports.
CASE REPORT
A 61-year-old women presented to the emergency department via emergency medical services with altered mental status and a Glasgow Coma Scale score of 8 out of 15. She was found down near multiple medication bottles, including diphenhydramine and dicyclomine. Her physical examination was consistent with anticholinergic toxicity with mydriasis, obtundation, and warm flushed skin. In addition to standard resuscitation, she received two doses of rivastigmine 3 mg via nasogastric tube. After the second dose she was alert and oriented. She was admitted to the intensive care unit and had a rivastigmine patch applied. She was deemed back to her baseline 27 h after presentation. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although the standard antidotal treatment for anticholinergic toxicity is physostigmine, there is a national shortage of this medication. In the absence of this standard antidote, it is reasonable for emergency physicians to use rivastigmine as an alternative treatment. This can be delivered orally or via nasogastric tube with dosing each hour until resolution of symptoms. Alternatively, in consultation with toxicology, it may be reasonable to use transdermal rivastigmine, as it provides consistent drug absorption for 24 h.
Topics: Humans; Female; Middle Aged; Rivastigmine; Physostigmine; Cholinergic Antagonists; Acetylcholinesterase; Cholinesterase Inhibitors; Antidotes; Anticholinergic Syndrome; Delirium; Transdermal Patch
PubMed: 37716903
DOI: 10.1016/j.jemermed.2023.06.008 -
Neurological Sciences : Official... Feb 2024Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common type of dementia. The early diagnosis of AD is an important factor for the... (Review)
Review
OBJECTIVE
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common type of dementia. The early diagnosis of AD is an important factor for the control of AD progression. Electroencephalography (EEG) can be used for early diagnosis of AD. Acetylcholinesterase inhibitors (AChEIs) are also used for the amelioration of AD symptoms. In this systematic review, we reviewed the effect of different AChEIs including donepezil, rivastigmine, tacrine, physostigmine, and galantamine on EEG patterns in patients with AD.
METHODS
PubMed electronic database was searched and 122 articles were found. After removal of unrelated articles, 24 articles were selected for the present study.
RESULTS
AChEIs can decrease beta, theta, and delta frequency bands in patients with AD. However, conflicting results were found for alpha band. Some studies have shown increased alpha frequency, while others have shown decreased alpha frequency following treatment with AChEIs. The only difference was the type of drug.
CONCLUSIONS
We found that studies reporting the decreased alpha frequency used donepezil and galantamine, while studies reporting the increased alpha frequency used rivastigmine and tacrine. It was suggested that future studies should focus on the effect of different AChEIs on EEG bands, especially alpha frequency in patients with AD, to compare their effects and find the reason for their different influence on EEG patterns. Also, differences between the effects of AChEIs on oligodendrocyte differentiation and myelination may be another important factor. This is the first article investigating the effect of different AChEIs on EEG patterns in patients with AD.
Topics: Humans; Cholinesterase Inhibitors; Alzheimer Disease; Donepezil; Rivastigmine; Galantamine; Acetylcholinesterase; Tacrine; Piperidines; Indans; Phenylcarbamates
PubMed: 37843690
DOI: 10.1007/s10072-023-07114-y -
Journal of Biomolecular Structure &... Dec 2023Alzheimer's disease (AD) is a complex neurodegenerative disorder involving cognitive dysfunction like short-term memory and behavioral changes as the disease progresses... (Review)
Review
Alzheimer's disease (AD) is a complex neurodegenerative disorder involving cognitive dysfunction like short-term memory and behavioral changes as the disease progresses due to other unaltered physiological factors. The solution for this problem is Multi-targeted Drugs (MTDs), which can affect multiple determinants to realize the multifunctional effects. Acetylcholinesterase (AChE) inhibitors donepezil, rivastigmine, galantamine, and N-methyl-D-aspartate (NMDA) receptor antagonist memantine are FDA-approved drugs used to treat AD symptomatically. The key objective of this review is to understand multitargeted bioactive natural molecules that could be considered as leads for further development as effective drugs for treating AD, along with understanding its pharmacology and structure-activity relationship (SAR). Understanding the molecular mechanism of the AD pathophysiology, the role of existing drugs, treatment of AD via amyloid beta (Aβ) plaque, and neurofibrillary tangle (NFT) inhibition by natural bioactive molecules were also discussed in the review. The current quest and recent advancements with natural bioactive compounds like physostigmine, resveratrol, curcumin, and catechins, along with the study of SAR, were reported in the present study. This review summarises the structural properties required for bioactive natural molecules to show anti-Alzheimer's activity by emphasizing on SAR of several bioactive natural molecules targeting various AD pathologies, their key molecular interactions that are critical for target specificity, their role as multitargeted ligands, used with adjunctive therapy for AD followed by related US patents granted recently. This article highlights the significance of the structural features of natural bioactive molecules in the treatment of AD and establishes a connection between them.Communicated by Ramaswamy H. Sarma.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Acetylcholinesterase; Cholinesterase Inhibitors; Structure-Activity Relationship
PubMed: 36579430
DOI: 10.1080/07391102.2022.2158136