Non-Dopaminergic Drugs for Motor Symptoms

2012 ◽  
pp. 881-892
Author(s):  
Pierre Burkhard ◽  
Francois Vingerhoets
Keyword(s):  
Motor Symptoms ◽  
Dopaminergic Drugs

scholarly journals Pramipexole and tolcapone alleviate thermal and mechanical nociception in naive rats.

Folia Medica ◽  
2021 ◽  
Vol 63 (3) ◽  
pp. 377-384
Author(s):  
Anita Mihaylova ◽  
Ilia Kostadinov ◽  
Nina Doncheva ◽  
Delian Delev ◽  
Hristina Zlatanova
Keyword(s):  
Neurodegenerative Disorder ◽  
Antinociceptive Effect ◽  
Positive Control ◽  
Motor Symptoms ◽  
Dopaminergic Drugs ◽  
Thermal Nociception ◽  
Dopaminergic Neurotransmission ◽  
Latent Time ◽  
Male Wistar Rats ◽  
Non Motor Symptoms

Introduction: Parkinson&rsquo;s disease (PD) is &#1072; neurodegenerative disorder characterized mainly by its motor symptoms. The non-motor symptoms including pain are increasingly recognized in the last few decades. Existing evidence suggests that the dopaminergic neurotransmission has an essential role in pain control. Aim: The aim of the present study was to investigate the antinociceptive effect of dopaminergic drugs pramipexole and tolcapone against chemical and thermal stimuli in naive rats. Materials and methods: Male Wistar rats divided into 8 groups (n=8): saline; diclofenac 25 mg/kg body weight (bw) (positive control); pramipexole 0.5; 1 and 3 mg/kg bw; tolacapone 5; 15 and 30 mg/kg bw. Paw pressure and plantar tests were performed. Paw withdrawal pressure and latent time were measured. Statistical analysis was done by SPSS 19. Results: In the paw pressure test, pramipexole, in a dose of 1 and 3 mg/kg bw and tolcapone in a dose of 30 mg/kg bw, increased significantly the latency at 1, 2, and 3 hours compared to saline (p<0.05). In the plantar test, only the highest dose of pramipexole reached significance at 3 hours compared to the control rats (p<0.05). In contrast to pramipexole the three experimental groups with tolcapone markedly increased the latent time at 1 and 3 hours compared to saline (p<0.05). Conclusions: Pramipexole and tolcapone reduce mechanical and thermal nociception in na&iuml;ve rats by enhancing dopaminergic neurotransmission at both spinal and supraspinal levels. In addition, tolcapone stimulates noradrenergic mediation which may contribute to its antinociceptive effect.

scholarly journals Can a Positive Allosteric Modulation of GABAergic Receptors Improve Motor Symptoms in Patients with Parkinson’s Disease? The Potential Role of Zolpidem in the Treatment of Parkinson’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Antonio Daniele ◽  
Francesco Panza ◽  
Antonio Greco ◽  
Giancarlo Logroscino ◽  
Davide Seripa
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Randomized Clinical Trials ◽  
Allosteric Modulation ◽  
Motor Symptoms ◽  
Dopaminergic Drugs ◽  
Internal Globus Pallidus ◽  
Gabaergic Neurotransmission ◽  
Increased Activity

At present, patients with advanced Parkinson’s disease (PD) are unsatisfactorily controlled by currently used anti-Parkinsonian dopaminergic drugs. Various studies suggest that therapeutic strategies based on nondopaminergic drugs might be helpful in PD. Zolpidem, an imidazopyridine widely used as sleep inducer, shows high affinity only forGABAAreceptors containing theα-1 subunit and facilitates GABAergic neurotransmission through a positive allosteric modulation ofGABAAreceptors. Various observations, although preliminary, consistently suggest that in PD patients zolpidem may induce beneficial (and sometimes remarkable) effects on motor symptoms even after single doses and may also improve dyskinesias. Since a high density of zolpidem binding sites is in the two main output structures of the basal ganglia which are abnormally overactive in PD (internal globus pallidus, GPi, and substantia nigra pars reticulata, SNr), it was hypothesized that in PD patients zolpidem may induce throughGABAAreceptors an inhibition of GPi and SNr (and, possibly, of the subthalamic nucleus also), resulting in an increased activity of motor cortical areas (such as supplementary motor area), which may give rise to improvement of motor symptoms of PD. Randomized clinical trials are needed in order to assess the efficacy, safety, and tolerability of zolpidem in treating motor symptoms of PD.

scholarly journals Could Small Heat Shock Protein HSP27 Be a First-Line Target for Preventing Protein Aggregation in Parkinson’s Disease?

2021 ◽  
Vol 22 (6) ◽  
pp. 3038
Author(s):  
Javier Navarro-Zaragoza ◽  
Lorena Cuenca-Bermejo ◽  
Pilar Almela ◽  
María-Luisa Laorden ◽  
María-Trinidad Herrero
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Heat Shock ◽  
Stress Proteins ◽  
Small Heat Shock Protein ◽  
Substantia Nigra Pars Compacta ◽  
Motor Symptoms ◽  
Dopaminergic Drugs ◽  
Non Motor Symptoms

Small heat shock proteins (HSPs), such as HSP27, are ubiquitously expressed molecular chaperones and are essential for cellular homeostasis. The major functions of HSP27 include chaperoning misfolded or unfolded polypeptides and protecting cells from toxic stress. Dysregulation of stress proteins is associated with many human diseases including neurodegenerative diseases, such as Parkinson’s disease (PD). PD is characterized by the presence of aggregates of α-synuclein in the central and peripheral nervous system, which induces the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and in the autonomic nervous system. Autonomic dysfunction is an important non-motor phenotype of PD, which includes cardiovascular dysregulation, among others. Nowadays, the therapies for PD focus on dopamine (DA) replacement. However, certain non-motor symptoms with a great impact on quality of life do not respond to dopaminergic drugs; therefore, the development and testing of new treatments for non-motor symptoms of PD remain a priority. Since small HSP27 was shown to prevent α-synuclein aggregation and cytotoxicity, this protein might constitute a suitable target to prevent or delay the motor and non-motor symptoms of PD. In the first part of our review, we focus on the cardiovascular dysregulation observed in PD patients. In the second part, we present data on the possible role of HSP27 in preventing the accumulation of amyloid fibrils and aggregated forms of α-synuclein. We also include our own studies, highlighting the possible protective cardiac effects induced by L-DOPA treatment through the enhancement of HSP27 levels and activity.

New Insights in the Pharmacotherapy of Psychosis: The Example of Parkinson's Disease Psychosis

2017 ◽  
Vol 41 (S1) ◽  
pp. S650-S650
Author(s):  
A. Fontaine ◽  
G. Radu
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Psychotic Disorders ◽  
Treatment Options ◽  
Cochrane Library ◽  
Psychotic Symptoms ◽  
Public Health Issue ◽  
Motor Symptoms ◽  
Visual Hallucinations ◽  
Dopaminergic Drugs

IntroductionWith 10 million of patients across the world, Parkinson's disease is the second most common form of neurodegeneration, after Alzheimer's. Among half of patients develop psychotic symptoms, such as visual hallucinations and delusions, which are correlated with higher rate of placement in nursing home, are difficult to treat and severely affect quality of life, making Parkinson's disease psychosis (PDP) a major public health issue.ObjectivesThe aim of this study is to identify treatment options that could be used to treat PDP and clarify underlying pathophysiology.MethodWe conducted a literature review on Pubmed, Goggle scholar and Cochrane library, using a combination of the following: “Parkinson's disease Psychosis” “visual hallucinations” “Pimavanserin” “Clozapine” “atypical anti-psychotics” 120 articles were screened.ResultsConsidering that hallucinations arise from overactivation of dopaminergic receptors, treatment options include reducing the dopaminergic drugs used to control motor symptoms; using atypical anti-psychotics such as Risperidone, Olanzapine, Quetiapine, which often results in the worsening of extra-pyramidal symptoms. Another option is the use of low doses of Clozapine, which has been proven efficient with no worsening of non-motor symptoms, suggesting the implication of other pathways, such as serotonin. Finally, Pimavanserin, a 5-HT2A receptor inverse agonist, without any dopaminergic activity, has been demonstrated to be effective in the treatment of PDP, well tolerated and easy to use.ConclusionSerotonin inverse agonists represent a major breakthrough in the pharmacotherapy of PDP, and may lead the way to changes in the treatment of schizophrenia and other psychotic disorders.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Classification and Characteristics of Pain Associated with Parkinson’s Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Marcelo Rezende Young Blood ◽  
Marcelo Machado Ferro ◽  
Renato Puppi Munhoz ◽  
Hélio Afonso Ghizoni Teive ◽  
Carlos Henrique Ferreira Camargo
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Characteristics ◽  
Neuropsychiatric Symptoms ◽  
Pain Modulation ◽  
Motor Symptoms ◽  
Nonmotor Symptoms ◽  
Dopaminergic Drugs ◽  
Lower Back ◽  
System Generation

Neuropsychiatric symptoms and pain are among the most common nonmotor symptoms of Parkinson’s disease (PD). The correlation between pain and PD has been recognized since its classic descriptions. Pain occurs in about 60% of PD patients, two to three times more frequent in this population than in age matched healthy individuals. It is an early and potentially disabling symptom that can precede motor symptoms by several years. The lower back and lower extremities are the most commonly affected areas. The most used classification for pain in PD defines musculoskeletal, dystonic, central, or neuropathic/radicular forms. Its different clinical characteristics, variable relationship with motor symptoms, and inconsistent response to dopaminergic drugs suggest that the mechanism underlying pain in PD is complex and multifaceted, involving the peripheral nervous system, generation and amplification of pain by motor symptoms, and neurodegeneration of areas related to pain modulation. Although pain in DP is common and a significant source of disability, its clinical characteristics, pathophysiology, classification, and management remain to be defined.

Spinal Dural Arteriovenous Fistula: Diagnosis and Treatment

2018 ◽  
Vol 1 (2) ◽  
Author(s):  
Nur Setiawan Suroto
Keyword(s):  
Spinal Cord ◽  
Arteriovenous Fistula ◽  
Vascular Malformation ◽  
Dural Arteriovenous Fistula ◽  
Motor Symptoms ◽  
Elderly Men ◽  
Spinal Dural Arteriovenous Fistula ◽  
Sensory Disturbances ◽  
Av Fistulas ◽  
Low Rate

Spinal dural arteriovenous (AV) fistulas are the most commonly encountered vascular malformation of the spinal cord and a treatable cause for progressive paraplegia or tetraplegia. They most commonly affected are elderly men and are classically found in the thoracolumbar region.Symptoms gradually progress or decline in a stepwise manner and are commonly associated with pain and sphincter disturbances. Surgical or endovascular disconnection of the fistula has a high success rate with a low rate of morbidity. Motor symptoms are most likely to improve after treatment, followed by sensory disturbances, and lastly sphincter disturbances.

Schizophrenia, Parkinson’s disease, and attention deficit hyperactivity disorder

2018 ◽  
Author(s):  
Richard J. Beninger
Keyword(s):  
Parkinson’S Disease ◽  
Attention Deficit Hyperactivity Disorder ◽  
Parkinson's Disease ◽  
Attention Deficit ◽  
Antipsychotic Treatment ◽  
Incentive Learning ◽  
Dopaminergic Drugs ◽  
Dopaminergic Neurotransmission ◽  
Hyperactivity Disorder ◽  
Incentive Value

Schizophrenia, Parkinson’s disease, and attention deficit hyperactivity disorder (ADHD) discusses how hyperactive dopaminergic neurotransmission appears to underlie schizophrenia’s positive symptoms, loss of dopaminergic neurons in adulthood leads to Parkinson’s disease, and dopamine neuron hypofunction in childhood and adolescence may underlie ADHD. Positive schizophrenia symptoms may arise from excessive incentive learning that is gradually lost with antipsychotic treatment. Declarative learning and memory may contribute to delusions based on excessive incentive learning. Loss of responsiveness to environmental stimuli in Parkinson’s may result from a decrease of their conditioned incentive value and inverse incentive learning. Conditioned incentive stimuli not encountered while in a state of decreased dopaminergic neurotransmission may retain their incentive value, producing apparent kinesia paradoxa. Dopamine hypofunction in juveniles does not lead to hypokinesia but may result in loss of incentive learning that focuses attention. Pro-dopaminergic drugs have a calming effect in ADHD, presumably because they reinstate normal incentive learning.

scholarly journals The Parkinson’s Real-World Impact Assessment (PRISM) Study: A European Survey of the Burden of Parkinson’s Disease in Patients and their Carers

2021 ◽  
pp. 1-15
Author(s):  
Eduardo Tolosa ◽  
Georg Ebersbach ◽  
Joaquim J. Ferreira ◽  
Olivier Rascol ◽  
Angelo Antonini ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Impact Assessment ◽  
Real World ◽  
European Countries ◽  
Life Questionnaire ◽  
Motor Symptoms ◽  
Non Motor Symptoms

Background: A greater understanding of the everyday experiences of people with Parkinson’s disease (PD) and their carers may help improve clinical practice. Objective: The Parkinson’s Real-world Impact assesSMent (PRISM) study evaluated medication use, health-related quality of life (HRQoL) and the use of healthcare resources by people with PD and their carers. Methods: PRISM is an observational cross-sectional study, in which people with PD and their carers completed an online survey using structured questionnaires, including the Parkinson’s Disease Quality of Life Questionnaire (PDQ-39), Non-Motor Symptoms Questionnaire (NMSQuest) and Zarit Burden Interview (ZBI). Results: Data were collected from 861 people with PD (mean age, 65.0 years; mean disease duration, 7.7 years) and 256 carers from six European countries. People with PD reported a large number of different co-morbidities, non-motor symptoms (mean NMSQuest score, 12.8), and impaired HRQoL (median PDQ-39 summary score, 29.1). Forty-five percent of people with PD reported at least one impulse control behaviour. Treatment patterns varied considerably between different European countries. Levodopa was taken in the last 12 months by 85.9% of participants, and as monotherapy by 21.8% . Carers, who were mostly female (64.8%) and the partner/spouse of the person with PD (82.1%), reported mild to moderate burden (mean ZBI total score, 26.6). Conclusions: The PRISM study sheds light on the lives of people with PD and those who care for them, re-emphasising the many challenges they face in everyday life. The study also provides insights into the current treatment of PD in Europe.

Sign in / Sign up

Export Citation Format

Share Document