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Parkinson drugs trials

Lawrence W Elmer, Jorge L Juncos, Carlos Singer, Daniel D Truong, Susan R Criswell, Sotirios Parashos, Larissa Felt, Reed Johnson, Rajiv Patni
BACKGROUND: Although levodopa is considered the most effective pharmacotherapy for motor symptoms of Parkinson's disease (PD), chronic use is associated with motor complications, including fluctuating response and unpredictable, involuntary movements called dyskinesia. ADS-5102 (amantadine) extended-release (ER) capsules (GOCOVRITM ) is a recent US FDA-approved treatment for dyskinesia in PD patients. ADS-5102 is a high-dose, ER formulation of amantadine, administered orally once daily at bedtime, that achieves high plasma drug concentrations throughout the day...
March 12, 2018: CNS Drugs
Agnieszka Zagorska, Anna Partyka, Adam Bucki, Alicja Gawalska, Anna Czopek, Maciej Pawlowski
BACKGROUND: The phosphodiesterase 10 (PDE10) family, identified in 1999, is mainly expressed in the brain, particularly in the striatum, within the medium spiny neurons, nucleus accumbens, and olfactory tubercle. Inhibitors of PDE10 (PDE10-Is) are a conceptually rational subject for medicinal chemistry with potential use in the treatment of psychiatric and neurodegenerative diseases. OBJECTIVE: This review is based on peer-reviewed published articles, and summarizes the cellular and molecular biology of PDE10 as a rational target for psychiatric and neurodegenerative drug discovery...
March 8, 2018: Current Medicinal Chemistry
Jose-Alberto Palma, Horacio Kaufmann
Dysfunction of the autonomic nervous system afflicts most patients with Parkinson disease and other synucleinopathies such as dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure, reducing quality of life and increasing mortality. For example, gastrointestinal dysfunction can lead to impaired drug pharmacodynamics causing a worsening in motor symptoms, and neurogenic orthostatic hypotension can cause syncope, falls, and fractures. When recognized, autonomic problems can be treated, sometimes successfully...
March 2018: Movement Disorders: Official Journal of the Movement Disorder Society
Paresh K Doshi
It has been three decades since the first application of deep brain stimulation (DBS) for tremors was described by Benabid. Over the years, the indications for the performance of DBS have been expanding. There are now more than 1,50,000 patients around the world who have undergone DBS for various disorders. The main appeal of DBS is in its reversibility and titratability. Though the initial interest in DBS was for pain, the main indications for DBS have been movement disorders. Despite its wide appeal and "perceived" advantage, United States Food and Drug Administration, the nodal agency for approving therapies, has been cautious and guarded in providing approvals...
March 2018: Neurology India
Andrew A Nierenberg, Sharmin A Ghaznavi, Isadora Sande Mathias, Kristen K Ellard, Jessica A Janos, Louisa G Sylvia
Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) is a protein that regulates metabolism and inflammation by activating nuclear receptors, especially the family of peroxisome proliferator-activated receptors (PPARs). PGC-1 alpha and PPARs also regulate mitochondrial biogenesis, cellular energy production, thermogenesis, and lipid metabolism. Brain energy metabolism may also be regulated in part by the interaction between PGC-1 alpha and PPARs. Because neurodegenerative diseases (Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis) and bipolar disorder have been associated with dysregulated mitochondrial and brain energy metabolism, PGC-1 alpha may represent a potential drug target for these conditions...
January 10, 2018: Biological Psychiatry
Amanda K Kitten, Sarah A Hallowell, Stephen R Saklad, Kirk E Evoy
Objective : Pimavanserin is the first United States Food and Drug Administration (FDA)-approved treatment for Parkinson's disease psychosis (PDP). This article reviews the safety, efficacy, and pharmacology data for pimavanserin and its role in therapy. Method of Research: Initial literature sources were identified via MEDLINE search (1946-September 2016) of pimavanserin and ACP-103 (original molecular designation). Reference review and search of and yielded additional studies. English-language studies of pimavanserin for PDP were evaluated...
February 1, 2018: Innovations in Clinical Neuroscience
Joseph H Friedman
Psychosis is a common problem for people treated for Parkinson's disease. The syndrome is quite stereotypic, with hallucinations being the most common, followed by delusions. While the hallucinations are usually not very bothersome, the delusions are typically paranoid in nature. Treatment is often, but not always, required. Areas covered: This article reviews the therapeutic approaches of this syndrome focusing on drug treatments used once contributory factors have been removed. This includes a review of the evidence supporting the use of clozapine and, most recently, pimavanserin, the first drug with antipsychotic efficacy that has no effect on dopamine...
March 1, 2018: Expert Opinion on Pharmacotherapy
Kannan Sridharan, Gowri Sivaramakrishnan
Sialorrhea is a common distress associated with certain neurological disorders. The aim of this study is to compare the pharmacological agents used for treating sialorrhea by network meta-analysis. Electronic databases were searched for randomized clinical trials comparing active drugs with either placebo or other active drugs. Total drooling scores was the primary outcome measure. Inverse variance heterogeneity model was used for both direct and mixed treatment comparison analysis. Twenty one studies were included in the systematic review and 15 in the meta-analysis...
February 20, 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Peng Feng, Xiangjian Zhang, Dongfang Li, Chenhui Ji, Ziyue Yuan, Ruifang Wang, Guofang Xue, Guanglai Li, Christian Hölscher
Type 2 diabetes mellitus (T2DM) is a risk factors for developing Parkinson's disease (PD). Insulin desensitization is observed in the brains of PD patients, which may be an underlying mechanism that promotes neurodegeneration. Incretin hormones are growth factors that can re-sensitize insulin signalling. We have previously shown that analogues of the incretins GLP-1 or GIP have neuroprotective effects in the MPTP mouse model of PD. Novel dual GLP-1/GIP receptor agonists have been developed as treatments for T2DM...
February 17, 2018: Neuropharmacology
Annalisa Pinna, Marcello Serra, Micaela Morelli, Nicola Simola
Adenosine is an endogenous purine nucleoside that regulates several physiological functions, at the central and peripheral levels. Besides, adenosine has emerged as a major player in the regulation of motor behavior. In fact, adenosine receptors of the A 2A subtype are highly enriched in the caudate-putamen, which is richly innervated by dopamine. Moreover, several studies in experimental animals have consistently demonstrated that the pharmacological antagonism of A 2A receptors has a facilitatory influence on motor behavior...
February 2, 2018: Journal of Neural Transmission
Alexandros Giannakis, Maria Chondrogiorgi, Christos Tsironis, Athina Tatsioni, Spiridon Konitsiotis
We investigated whether there is a linear relationship between levodopa (LD) dose and treatment duration, and the development of levodopa-induced dyskinesia (LID) among patients with early untreated Parkinson's disease (PD). We performed a meta-analysis of randomized-controlled trials (RCTs) comparing LD monotherapy to any other antiparkinsonian treatment in early PD patients. Meta-regressions were conducted including as covariates the effects of LD dose, treatment duration, and age. We further proceeded in subgroup analyses based on the type of medications in the non-LD monotherapy (control) group and on whether patients in the control group received additional levodopa or not...
January 19, 2018: Journal of Neural Transmission
Bao-Dong Li, Jing-Jun Cui, Jia Song, Ce Qi, Pei-Feng Ma, Ya-Rong Wang, Jing Bai
BACKGROUND/AIMS: A network meta-analysis is used to compare the efficacy of ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control, for non-motor symptoms in Parkinson's disease (PD). METHODS: PubMed, Embase and the Cochrane Library were searched from their establishment dates up to January 2017 for randomized controlled trials (RCTs) investigating the efficacy of the above ten drugs on the non-motor symptoms of PD...
January 15, 2018: Cellular Physiology and Biochemistry
Fábio G Teixeira, Miguel F Gago, Paulo Marques, Pedro Silva Moreira, Ricardo Magalhães, Nuno Sousa, António J Salgado
The loss of dopaminergic neurons (DAn) and reduced dopamine (DA) production underlies the reasoning behind the gold standard treatment for Parkinson's disease (PD) using levodopa (L-DOPA). Recently licensed by the European Medicine Agency (EMA) and US Food and Drug Administration (FDA), safinamide [a monoamine oxidase B (MOA-B) inhibitor] is an alternative to L-DOPA; as we discuss here, it enhances dopaminergic transmission with decreased secondary effects compared with L-DOPA. In addition, nondopaminergic actions (neuroprotective effects) have been reported, with safinamide inhibiting glutamate release and sodium/calcium channels, reducing the excitotoxic input to dopaminergic neuronal death...
March 2018: Drug Discovery Today
Willi Cawello, Marina Braun, Jens-Otto Andreas
BACKGROUND AND OBJECTIVE: Pharmacokinetic studies using deconvolution methods and non-compartmental analysis to model clinical absorption of drugs are not well represented in the literature. The purpose of this research was (1) to define the system of equations for description of rotigotine (a dopamine receptor agonist delivered via a transdermal patch) absorption based on a pharmacokinetic model and (2) to describe the kinetics of rotigotine disposition after single and multiple dosing...
January 13, 2018: European Journal of Drug Metabolism and Pharmacokinetics
Neil Barua, Steven Gill
There has been substantial research interest in delivering therapeutic neurotrophic factors directly to the brain for the treatment of Parkinson's Disease (PD) and other movement disorders. Direct infusion of glial cell-line derived neurotrophic factor has been investigated in both pre-clinical models and clinical trials. In this chapter we discuss past and present research investigating the potential of direct drug delivery to the brain for the treatment of PD and other movement disorders.
2018: Progress in Neurological Surgery
Young Goo Kim, Eun Jung Kweon, Won Seok Chang, Hyun Ho Jung, Jin Woo Chang
Transcranial magnetic resonance-guided focused ultrasound (MRgFUS) surgery has recently gained favor as a novel, noninvasive alternative to conventional neurosurgery. In contrast to traditional ablative interventions, transcranial MRgFUS surgery is entirely imaging-guided and uses continuous temperature measurements at the target and surrounding tissue taken in real-time. Unlike Gamma Knife radiosurgery, MRgFUS surgery can make a lesion immediately and does not use ionizing radiation. Moreover, since no metallic device is implanted, MR imaging-based diagnosis is not restricted throughout life...
2018: Progress in Neurological Surgery
Chia-Hsiang Chan, Hung-Yu Chan, Yen-Ching Chen
Aripiprazole is a second-generation antipsychotics, acting as a partial dopamine D2 receptor agonist. Previous studies on aripiprazole for tardive dyskinesia (TD) treatment were limited and inconclusive. This study was aimed to examine the effectiveness of aripiprazole in psychotic patients with a pre-existing TD. This was an open-label 24-week prospective cohort study conducted in a public mental hospital in Northern Taiwan from January 2009 to February 2010.Psychotic patients were cross-titrated of prior antipsychotics with aripiprazole, and the severity of TD was assessed at baseline and at weeks 2, 4, 8, 12, 16, 20, and 24...
January 10, 2018: International Clinical Psychopharmacology
Caroline A MacCallum, Ethan B Russo
Cannabis has been employed medicinally throughout history, but its recent legal prohibition, biochemical complexity and variability, quality control issues, previous dearth of appropriately powered randomised controlled trials, and lack of pertinent education have conspired to leave clinicians in the dark as to how to advise patients pursuing such treatment. With the advent of pharmaceutical cannabis-based medicines (Sativex/nabiximols and Epidiolex), and liberalisation of access in certain nations, this ignorance of cannabis pharmacology and therapeutics has become untenable...
March 2018: European Journal of Internal Medicine
Clementine Stuijt, Fatma Karapinar-Çarkit, Bart van den Bemt, Teus van Laar
INTRODUCTION: Patients with Parkinson disease (PD) use multiple drugs. This pill burden with consequent poor adherence may cause worsening of motor symptoms and drug-related problems. Therefore, a multifaceted pharmacist-led intervention program was designed to improve adherence, motor-functioning, and quality of life (QoL) in PD patients. METHODS: This prospective pilot study was performed in an outpatient PD clinic, where usual care was compared with stepwise introduction of 3 interventions: unit dose packaging (UDP), Parkinson KinetiGraph (PKG), and pharmacist-led medication review (MR)...
January 3, 2018: Clinical Neuropharmacology
Hirotaka Iwaki, Rina Ando, Noriyuki Miyaue, Satoshi Tada, Tomoaki Tsujii, Hayato Yabe, Noriko Nishikawa, Masahiro Nagai, Masahiro Nomoto
BACKGROUND: Epidemiological studies have repeatedly reported that increased serum urate level is associated with a slower progress of Parkinson's disease (PD). The urate precursor, inosine, raises the serum urate level and is therefore a candidate for a disease modifying treatment. However, an elevated serum urate level is a risk factor for gout, urolithiasis, and cardiovascular diseases. Although there have been previous clinical studies, the use of inosine in a clinical setting is still limited, and its safety is unclear, especially in an Asian population...
December 15, 2017: Journal of the Neurological Sciences
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