- Old Drugs, New Delivery Systems in Parkinson's Disease. [Review]
- DADrugs Aging 2019 Jun 03
- Levodopa is the mainstay of treatment in Parkinson's disease (PD). As the disease progresses, variations in plasma levodopa levels lead to motor fluctuations. The common reasons behind variations in …
Levodopa is the mainstay of treatment in Parkinson's disease (PD). As the disease progresses, variations in plasma levodopa levels lead to motor fluctuations. The common reasons behind variations in the plasma levels include delayed gastric emptying, small intestinal bacterial overgrowth, protein interaction with levodopa absorption, and limited oral bioavailability of levodopa. Efforts to find newer delivery systems for older drugs to avoid the problems associated with oral delivery of medications are continuing. This review aims to provide up-to-date information about the newer delivery options for drugs used for PD and provides a summary of infusion therapy with apomorphine, modifications to other dopamine agonists, various oral formulations of carbidopa/levodopa, inhaled levodopa, intrajejunal infusion of levodopa, and sublingual apomorphine. The advantages, dose, and adverse effects of each treatment modality are reviewed. We also discuss several drugs under investigation, such as the subcutaneous carbidopa/levodopa infusion and subcutaneous rotigotine.
- Language as a Threat: Multimodal Evaluation and Interventions for Overwhelming Linguistic Anxiety in Severe Aphasia. [Journal Article]
- FPFront Psychol 2019; 10:678
- Linguistic anxiety (LA) is an abnormal stress response induced by situations that require the use of verbal behavior, and it is accentuated during language testing in persons with aphasia (PWA). The …
Linguistic anxiety (LA) is an abnormal stress response induced by situations that require the use of verbal behavior, and it is accentuated during language testing in persons with aphasia (PWA). The presence of LA in PWA may jeopardize the interpretation of cognitive evaluations, leading to biased conclusions about the severity of the language alteration and the effectiveness of the treatments. In the present study, we report the case of a woman (Mrs. A) with severe chronic mixed transcortical aphasia due to left frontal and parietal hemorrhages that partially spared the perisylvian area. Mrs. A was treated with the dopamine agonist Rotigotine alone and combined with Intensive Language-Action Therapy (ILAT). Complementary evaluations included autonomic reactivity during the performance of different language tasks, resting state functional magnetic resonance imaging (rs-fMRI) and [18F]-fluorodeoxyglucose positron emission tomography (18F-FDG-PET). We found that formal language testing in a clinical setting triggered a dramatic increase of automatic echolalia, perseverations and frustration, making the task completion difficult. The treatment improved aphasia, but gains were more robust when evaluation was performed by Mrs. A's husband at home than by clinicians. Autonomic evaluation under Rotigotine revealed higher reactivity during tasks tapping an impaired function in comparison with a task evaluating a preserved function (verbal repetition). Baseline 18F-FDG-PET analysis showed decreased metabolic activity in left limbic-paralimbic areas, whereas rs-fMRI revealed compensatory activity in the right hemisphere. We also analyzed the different factors (e.g., premorbid personality traits, task difficulty) that may have contributed to LA in Mrs. A during language testing. Our findings emphasize the usefulness of implicating adequately trained laypersons in the evaluation and treatment of PWA showing LA. Further studies using multidimensional evaluations are needed to disentangle the interplay between anxiety and abnormal language as well as the neural mechanisms underpinning LA in PWA.
- Safety and efficacy of Rotigotine in hospedalized patients with Vascular Parkinsonism aged 75 and older: effects on movement, praxis capacities, time-space orientation, quality of life and adherence to medical therapy. [Journal Article]
- ABActa Biomed 2019 May 23; 90(2):248-250
- In hospitals without stroke unit Department, the patients with acute ischemic stroke are stabilized in First Aid and sent to the Department of Internal Medicine. During the hospedalization period the…
In hospitals without stroke unit Department, the patients with acute ischemic stroke are stabilized in First Aid and sent to the Department of Internal Medicine. During the hospedalization period the patients undergo medical therapy for the stabilization of hemodynamic parameters and instrumental examinations for the determination of cardiovascular risk and thromboembolic evaluation. All patients are subjected to multidimensional evaluation of cognitive, praxis capacities, spatial-temporal orientation, quality of life and adherence to medical therapy. The aim of this study is evaluate the effect of Rotigotine patch on the impairment of neuro-cognitive capacity throught a continuous dopaminergic stimulation with transdermal administration. We have observed 19 patients (10 male and 9 female with range age 75-92 yrs) with Acute Ischemic Stroke stabilized in First Aid Depatment. The outcomes were the neurological changes from the baseline to 7 days in the clinical summury score on MMSE (on a scale from 0 to 30, with higher scores indicating fewer symtoms and lower physical limitations), Morinsky scale (on scale from 0 to 8, indicating adherence to therapy) and swallowing test (acts/minute). During the first week the patients were undergone to treatment with rotigotine 2 mg/24 hours. At the end of the treatment we obtained a statistically significant correlation about improvement of MMSE, Morinsky scale and swallowing test from a basal value. Rotigotine transdermal patches could be a new useful approach in the treatment of elderly hospetalized patients with acute ischaemic stroke correlated with cognitive impairment. Data shown that low dose of rotigotine patch could improves cognitive and praxis functions and therefore the quality of life of the hospitalized elderly patients. Rotigotine was effective and well-tolerated when used in routine clinical practice. Our data gave comfortable results but further evaluation are needed to have conclusive results.
- Quantitative Comparison of the Efficacies of 5 First-Line Drugs for Primary Restless Leg Syndrome. [Journal Article]
- JCJ Clin Pharmacol 2019 May 20
- Comparative analyses of the efficacies of dopaminergic agonists (pramipexole, ropinirole, and rotigotine patch) and α-2-δ ligands (gabapentin enacarbil and pregabalin) for treatment of primary restle…
Comparative analyses of the efficacies of dopaminergic agonists (pramipexole, ropinirole, and rotigotine patch) and α-2-δ ligands (gabapentin enacarbil and pregabalin) for treatment of primary restless leg syndrome (RLS) are lacking because of the few head-to-head clinical trials. A model-based meta-analysis approach was employed to quantitatively compare the efficacies of these 5 first-line RLS drugs. Longitudinal efficacy data of RLS drugs were collected from published eligible literature. Mean changes in both the International Restless Leg Syndrome Study Group (IRLS) rating scale and Clinical Global Impression Improvement (CGI-I) scale response rate were analyzed. A study-level population pharmacodynamic model was used to fit the dose-effect relationship and to describe the therapeutic effect over time for RLS drugs and placebo, and the typical efficacies of these drugs were compared. The onset of action was rapid for RLS drugs. In the placebo group, typical maximum IRLS reduction (Emax,IRLS) and CGI-I response rate (Emax,CGI-I) were -9.34 points and 48.2%, respectively. After deducting placebo effects, we found that the baseline IRLS score was significantly correlated with the Emax,IRLS of dopaminergic agonists. Typical Emax,IRLS of dopaminergic agonists was expressed as - 7.7 - 0.682 × (baseline IRLS score - 24) points. Typical Emax,IRLS values of pregabalin and gabapentin enacarbil were -5.95 points and -4.00 points, respectively. The therapeutic effect of dopaminergic agonists was found to be associated with baseline symptom severity. In RLS patients with more severe symptoms, the therapeutic effect of dopaminergic agonists tended to be better than that of α-2-δ ligands.
- Dopamine D2/D3 receptor agonists attenuate PTSD-like symptoms in mice exposed to single prolonged stress. [Journal Article]
- NNeuropharmacology 2019 May 11; 155:1-9
- Medications that enhance dopaminergic neurotransmission can be useful in the pharmacotherapy of posttraumatic stress disorder (PTSD), which manifests as fearful memory retrieval, anxiety and depressi…
Medications that enhance dopaminergic neurotransmission can be useful in the pharmacotherapy of posttraumatic stress disorder (PTSD), which manifests as fearful memory retrieval, anxiety and depression. We examined the effects of subchronic (15 days) treatment with select dopaminergic medications, including bromocriptine, modafinil, dihydrexidine, rotigotine and pramipexole, in a mouse model of PTSD induced by single prolonged stress (mSPS). The potential antidepressant-like and anxiolytic effects of the medications were measured by the forced swim test (FST) and the elevated plus maze (EPM) test, respectively. In addition, we studied the effects of these medications on memory retrieval in an auditory fear conditioning (FC) test, on ultrasonic vocalizations (USVs) induced by restraint stress, and on spontaneous locomotor activity (SLA). We report that a single exposure to a severe and complex set of stressors several days before testing increased immobility time in the FST and freezing in the FC paradigm and reduced the time spent in the open arms of the EPM. The stressed mice also displayed increased USVs, especially the short type. While none of the tested dopamine-mimetics exhibited anxiolytic-like effects, rotigotine produced antidepressant-like activity specifically in the mSPS-exposed animals. Moreover, both rotigotine and pramipexole shortened the duration of freezing in the fear conditioning test, but only in the mSPS-exposed mice. This study supports the hypothesis that the activation of dopaminergic D2/D3 receptors may be a promising pharmacotherapy for PTSD.
- Effects of rotigotine and rotigotine extended-release microsphere therapy on myocardial ischemic injury in mice. [Journal Article]
- EJEur J Pharm Sci 2019 Jun 15; 134:1-6
- Rotigotine is a dopamine receptor agonist that can improve motor function in Parkinson's disease (PD) patients. Rotigotine extended-release microsphere (RoMS) is an extended-release intramuscular for…
Rotigotine is a dopamine receptor agonist that can improve motor function in Parkinson's disease (PD) patients. Rotigotine extended-release microsphere (RoMS) is an extended-release intramuscular formulation that exhibits a sustained release of rotigotine over a 14-day period. The clinical trials of RoMS has been carried out in USA and China. The purpose of this study is to observe the effects of RoMS therapy on myocardial ischemic injury in mice, to know whether RoMS alleviate or deteriorate the myocardial ischemic injury while PD patient has onset of myocardial ischemia concurrent after administered with RoMS. A mouse model of myocardial ischemia was established using isoproterenol, and mice were pretreated with rotigotine or RoMS before inducing myocardial ischemic injury. The effects of rotigotine or RoMS therapy on the degree of myocardial ischemic injury were studied by evaluating troponin I level, creatine kinase-MB (CK-MB) activity, and histopathological changes in cardiomyocytes. The dopamine receptor blocker chlorpromazine was used to further investigate the effects of rotigotine or RoMS on myocardial ischemic injury. Furthermore, serum rotigotine concentrations were also assayed. When myocardial ischemia occurred during rotigotine or RoMS administration, troponin I level and CK-MB activity were decreased, and ischemia-induced histopathological changes in cardiomyocytes were alleviated. The effects of rotigotine were maintained only 12 h and after that no protective effect was observed. RoMS releases continuously into the circulation after intramuscular injection. The cardioprotective effects of RoMS were maintained 14 days after a single RoMS administration. When combined with chlorpromazine, the protective effects of rotigotine on myocardial ischemic injury were eliminated, and the protective effects of RoMS were also partially abolished. In the animal model of myocardial ischemia, pretreatment with rotigotine or RoMS does not deteriorate, but can alleviate cardiomyocyte injury. Furthermore, RoMS pretreatment show long-term and continuous protective effects on cardiomyocyte injury. RoMS therapy in PD patients at high risk for cardiovascular diseases may attenuate the degree of cardiomyocyte injury caused by ischemia.
- Effect of using a wearable device on clinical decision-making and motor symptoms in patients with Parkinson's disease starting transdermal rotigotine patch: A pilot study. [Journal Article]
- PRParkinsonism Relat Disord 2019 Jan 28
- CONCLUSIONS: Continuous, objective, motor symptom monitoring using a wearable biosensor as an adjunct to standard care may enhance clinical decision-making, and may improve outcomes in PD patients starting rotigotine.
- Creativity related to dopaminergic treatment: A multicenter study. [Journal Article]
- PRParkinsonism Relat Disord 2019 Feb 22
- Impulse control disorder (ICD), including pathological gambling, hypersexuality, and compulsive shopping has been linked to dopaminergic treatment, especially treatment with dopamine agonists (DAs). …
Impulse control disorder (ICD), including pathological gambling, hypersexuality, and compulsive shopping has been linked to dopaminergic treatment, especially treatment with dopamine agonists (DAs). However, patients with Parkinson's disease (PD) may experience enhanced creativity during DA therapy, often manifesting as newfound artistic pursuits. Though ICD is very well recognized in the literature, enhanced creativity remains underreported, probably because, unlike ICD, enhanced creativity is often positive and rarely disruptive for patients and relatives. We studied 21 patients (20 patients with PD and one patient with restless-legs syndrome) with enhanced creativity. These individuals engaged in artistic activities after dopaminergic treatment; all but one were treated with DA (pramipexole, 14/21; ropinirole, 4/21; rotigotine 2/21). Most patients preferred painting as their main activity, but many were engaged in several activities, usually in combination. We hypothesize that by facilitating a stimulating environment for parkinsonian patients, this positive phenomenon may present more frequently.
- Pharmacogenetic Profile and the Occurrence of Visual Hallucinations in Patients With Sporadic Parkinson's Disease. [Journal Article]
- JCJ Clin Pharmacol 2019; 59(7):1006-1013
- Visual hallucinations are significant nonmotor symptoms in the course of treatment of Parkinson's disease. Previous studies have shown that the interindividual variability and pharmacogenetic profile…
Visual hallucinations are significant nonmotor symptoms in the course of treatment of Parkinson's disease. Previous studies have shown that the interindividual variability and pharmacogenetic profile of Parkinson's disease patients seem to influence the occurrence of visual hallucinations. In our study, we investigated a possible relationship of sequence variants in DRD1, DRD2, DRD3, DAT1, and COMT genes with the presence of visual hallucinations in Parkinson's disease patients. A total of 224 Brazilian patients from the Pro-Parkinson service at the Clinical Hospital of the University of Pernambuco, diagnosed with sporadic Parkinson's disease, were enrolled. Parkinson's disease patients were divided into 2 groups based on the presence or absence of visual hallucinations. The sequence variants for DRD1, DRD2, DRD3, DAT1, and COMT were determined through the polymerase chain reaction-restriction fragment length polymorphism technique. Multiple Poisson regression analyses showed that individuals carrying the DRD3 Ser/Ser and Ser/Gly genotypes presented increased prevalence ratios of visual hallucinations (9.7-fold and 4.4-fold, respectively; P < .001). Regarding DAT1 rs28363170, there was a 9.82-fold increase in the prevalence ratio in patients with the 10/11 genotype, 8.78-fold for the 10/8 genotype, and 2.44-fold for the 9/8 genotypes (P < .001, for all). In addition, visual hallucinations were also associated with use of transdermal patches with rotigotine (PR, 3.7; 95%CI, 1.2-10.9; P = .017) and rasagiline (PR, 2.8; 95%CI, 1.3-6.0; P = .006). Our results suggest that the genetic variants DRD3 and DAT1, along with other therapeutic confounders, may influence the prevalence ratio of visual hallucinations.
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- Contact leukoderma induced by rotigotine transdermal patch (Neupro®). [Journal Article]
- EJEur J Dermatol 2019 04 01; 29(2):215-217