Background: Dopamine replacement therapies (levodopa, dopamine receptor agonists, anticholinergics, monoamine oxidase B inhibitors, and catechol-O-methyltransferase inhibitors) remain the cornerstones of therapeutic interventions for Parkinson's disease (PD). Despite the treatment options for PD symptoms, a cure remains elusive. An optimal treatment would be one that combined relief in both motor and nonmotor symptoms with neuroprotective properties. Safinamide is an investigational drug for PD currently in development as add-on therapy to both dopamine agonists and levodopa. Safinamide is a unique molecule with a novel mode of action, targeting both dopaminergic and glutaminergic systems, and potentially provides motor symptom control. Preliminary results from experimental models suggest potential neuroprotective effects. Studies on the potential effects on nonmotor symptoms are ongoing. Objective: To review the mechanism of action and pharmacokinetics, and to evaluate the available clinical safety and efficacy results of safinamide. Methods: A search of the electronic database MEDLINE (PubMed, no time limits) was performed on 14 December 2007. The full text of all citations was obtained for review. Furthermore, two abstracts on safinamide published as proceedings of a European conference were reviewed. Results/conclusion: Safinamide is a promising investigational drug for PD with a novel mode of action. Early reports confirm the potential efficacy of safinamide in PD. Further studies on potential effects on cognition and neuroprotection are needed. 相似文献
This review briefly summarizes the information on the molecular mechanisms of action, pharmacokinetic profiles and drug interactions of novel (third-generation) antiepileptic drugs, including brivaracetam, carabersat, carisbamate, DP-valproic acid, eslicarbazepine, fluorofelbamate, fosphenytoin, ganaxolone, lacosamide, losigamone, pregabalin, remacemide, retigabine, rufinamide, safinamide, seletracetam, soretolide, stiripentol, talampanel, and valrocemide. These novel antiepileptic drugs undergo intensive clinical investigations to assess their efficacy and usefulness in the treatment of patients with refractory epilepsy. 相似文献
Introduction: The major unmet needs in the medical treatment of Parkinson disease (PD) are reduction of motor side effects from dopaminergic drugs, management of non-motor symptoms and disease modification.
Areas covered: Motor fluctuations and OFF periods are a significant determinant of quality of life in PD and reducing their duration and severity can significantly improve motor function. This aim may be partly facilitated by the development of effective adjunctive drugs for dopamine replacement. Safinamide (Xadago), which is a first generation anticonvulsant, has pharmacological properties which are of interest in the context of neurodegenerative diseases, leading to research into its potential as an adjunct to levodopa in PD.
Expert opinion: Although its mechanism has not been fully defined, safinamide provides enhanced symptom control of motor function in advanced PD and improves quality of life. 相似文献
Epilepsy affects ≤ 1% of the world's population. Antiepileptic drugs (AEDs) are the mainstay of treatment, although more than a third of patients are not rendered seizure free with existing medications. Uncontrolled epilepsy is associated with increased mortality and physical injuries, and a range of psychosocial morbidities, posing a substantial economic burden on individuals and society. Limitations of the present AEDs include suboptimal efficacy and their association with a host of adverse reactions. Continued efforts are being made in drug development to overcome these shortcomings employing a range of strategies, including modification of the structure of existing drugs, targeting novel molecular substrates and non-mechanism-based drug screening of compounds in traditional and newer animal models. This article reviews the need for new treatments and discusses some of the emerging compounds that have entered clinical development. The ultimate goal is to develop novel agents that can prevent the occurrence of seizures and the progression of epilepsy in at risk individuals. 相似文献
Levodopa remains the most potent drug to treat motor symptoms in Parkinson’s disease (PD); however, motor fluctuations and levodopa-induced dyskinesia that occur with long-term use restrict some of its therapeutic value. Despite these limitations, the medical treatment of PD strives for continuous relief of symptoms using different strategies throughout the course of the illness: increasing the half-life of levodopa, using ‘levodopa-sparing agents’ and adding non-dopaminergic drugs. New options to ‘improve’ delivery of levodopa are under investigation, including long-acting levodopa, nasal inhalation and continuous subcutaneous or intrajejunal administration of levodopa. Long-acting dopamine agonists were recently developed and are undergoing further comparative studies to investigate potential superiority over the immediate-release formulations. Non-dopaminergic drugs acting on adenosine receptors, cholinergic, adrenergic, serotoninergic and glutamatergic pathways are newly developed and many are being evaluated in Phase II and Phase III trials. This article focuses on promising novel therapeutic approaches for the management of PD motor symptoms and motor complications. We will provide an update since 2011 on new formulations of current drugs, new drugs with promising results in Phase II and Phase III clinical trials, old drugs with new possibilities and some new potential strategies that are currently in Phase I and II of development (study start date may precede 2011 but are included as study is still ongoing or full data have not yet been published). Negative Phase II and Phase III clinical trials published since 2011 will also be briefly mentioned. 相似文献