Recent patents on CNS drug discovery最新文献

{"title":"A survey of recent patents on CB2 agonists in the management of pain.","authors":"Gabriele Murineddu,&nbsp;Battistina Asproni,&nbsp;Gerard A Pinna","doi":"10.2174/157488912798842214","DOIUrl":"https://doi.org/10.2174/157488912798842214","url":null,"abstract":"<p><p>Pain, a homeostatic and protective mechanism which can go awry in disease states and therefore needs treatment, is a complex and differentiated sensorial perception which may be classified as physiological, inflammatory and neuropathic. Chronic pain represents a major health problem throughout the world, thus several companies and researchers have embarked on the search for new drugs and targets to treat the disease. The different types of receptors in the CNS involved in the mediation of analgesia include the cannabinoid receptors: in particular, CB2 modulators seem to represent a new potential class of analgesic. This review covers recent patents and advances in CB2 agonist studies in the management of pain.</p>","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"7 1","pages":"4-24"},"PeriodicalIF":0.0,"publicationDate":"2012-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/157488912798842214","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30415225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid-based nanocarriers for CNS-targeted drug delivery.","authors":"Maria-Rita Micheli,&nbsp;Rodolfo Bova,&nbsp;Alessandro Magini,&nbsp;Mario Polidoro,&nbsp;Carla Emiliani","doi":"10.2174/157488912798842241","DOIUrl":"https://doi.org/10.2174/157488912798842241","url":null,"abstract":"<p><p>Nanotechnology exerts an increasing impact on the development of more effective tools for the diagnosis and treatment of human diseases. This applies in particular to central nervous system (CNS) disorders. Development of therapeutics for CNS is, in fact, one of the most challenging areas in drug development, mainly due to the presence of the blood-brain barrier (BBB) which separates the blood from the cerebral parenchyma thus limiting the brain uptake of the vast majority of neurotherapeutic agents. Among the several strategies which have been developed over the last years in order to overcome this problem, nanotechnology-based approaches have gained increasing attention as the most promising strategies for CNS targeted drug delivery. Nanocarriers offer several advantages such as the possibility to maintain drug levels in a therapeutically desirable range, as well as the increase of half-lives, solubility, stability and permeability of drugs. Furthermore, the system can be designed in such a way as to release the drug in a controlled way or in a triggered way. This review focuses on lipid-based nanocarriers and more specifically on liposomes, lipid-core micelles, and lipid nanocapsules, and provides an update on their composition and use, including recent patents in the field.</p>","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"7 1","pages":"71-86"},"PeriodicalIF":0.0,"publicationDate":"2012-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/157488912798842241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30417356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In this issue of Recent Patents on CNS Drug Discovery, focus is laid upon the potential development of new therapeutic drugs for neurological and affective disorders through targeting the endocannabinoid system. Introduction.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"7 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2012-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30501420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial [hot topic: cannabinoid receptors ligands (guest editor: Gabriele Murineddu)].","authors":"G Murineddu","doi":"10.2174/157488912798842232","DOIUrl":"https://doi.org/10.2174/157488912798842232","url":null,"abstract":"","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"7 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2012-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/157488912798842232","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30415224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibitors of the endocannabinoid-degrading enzymes, or how to increase endocannabinoid's activity by preventing their hydrolysis.","authors":"Marion Feledziak,&nbsp;Didier M Lambert,&nbsp;Jacqueline Marchand-Brynaert,&nbsp;Giulio G Muccioli","doi":"10.2174/157488912798842223","DOIUrl":"https://doi.org/10.2174/157488912798842223","url":null,"abstract":"<p><p>Endocannabinoids are lipid transmitters binding and activating the cannabinoid receptors. Both cannabinoid receptors and endocannabinoids, such as 2-arachidonoylglycerol and anandamide, have been shown to control numerous physiological and pathological processes, including in the central nervous system. Thus regulating endocannabinoid levels in-vivo represents an interesting therapeutic perspective in several CNS-related diseases. To date four enzymes - Fatty Acid Amide Hydrolase (FAAH), N-Acylethanolamine-hydrolyzing Acid Amidase (NAAA), Monoacylglycerol Lipase (MAGL), α/β-Hydrolase Domain 6 (ABHD6) - were shown to control endocannabinoid levels in tissues or in intact cells. While the searches for NAAA and ABHD6 inhibitors are still in their beginning, a growing number of selective and potent inhibitors are now available to inhibit FAAH and MAGL activities. Here, based on the literature and patent literature, we review the compounds of the different chemical families that have been developed to inhibit these enzymes, with a special emphasis on FAAH and MAGL inhibitors.</p>","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"7 1","pages":"49-70"},"PeriodicalIF":0.0,"publicationDate":"2012-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/157488912798842223","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30415227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabinoids: novel medicines for the treatment of Huntington's disease.","authors":"Onintza Sagredo,&nbsp;M Ruth Pazos,&nbsp;Sara Valdeolivas,&nbsp;Javier Fernandez-Ruiz","doi":"10.2174/157488912798842278","DOIUrl":"https://doi.org/10.2174/157488912798842278","url":null,"abstract":"<p><p>Cannabinoid pharmacology has experienced a notable increase in the last 3 decades which is allowing the development of novel cannabinoid-based medicines for the treatment of different human pathologies, for example, Cesamet® (nabilone) or Marinol® (synthetic Δ9-tetrahydrocannabinol for oral administration) that were approved in 80s for the treatment of nausea and vomiting associated with chemotherapy treatment in cancer patients and in 90s for anorexiacachexia associated with AIDS therapy. Recently, the british company GW Pharmaceuticals plc has developed an oromucosal spray called Sativex®, which is constituted by an equimolecular combination of Δ9-tetrahydrocannabinol- and cannabidiol- enriched botanical extracts. Sativex® has been approved for the treatment of specific symptoms (i.e. spasticity and pain) of multiple sclerosis patients in various countries (i.e. Canada, UK, Spain, New Zealand). However, this cannabis- based medicine has been also proposed to be useful in other neurological disorders given the analgesic, antitumoral, anti-inflammatory, and neuroprotective properties of their components demonstrated in preclinical models. Numerous clinical trials are presently being conducted to confirm this potential in patients. We are particularly interested in the case of Huntington's disease (HD), an autosomal-dominant inherited disorder caused by an excess of CAG repeats in the genomic allele resulting in a polyQ expansion in the encoded protein called huntingtin, and that affects primarily striatal and cortical neurons thus producing motor abnormalities (i.e. chorea) and dementia. Cannabinoids have been studied for alleviation of hyperkinetic symptoms, given their inhibitory effects on movement, and, in particular, as disease-modifying agents due to their anti-inflammatory, neuroprotective and neuroregenerative properties. This potential has been corroborated in different experimental models of HD and using different types of cannabinoid agonists, including the phytocannabinoids present in Sativex®, and we are close to initiate a clinical trial with this cannabis-based medicine to evaluate its capability as a disease-modifying agent in a population of HD patients. The present review will address all preclinical evidence supporting the potential of Sativex® for the treatment of disease progression in HD patients. The article presents some promising patents on the cannabinoids.</p>","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"7 1","pages":"41-8"},"PeriodicalIF":0.0,"publicationDate":"2012-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/157488912798842278","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30415226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent approaches targeting beta-amyloid for therapeutic intervention of Alzheimer's disease.","authors":"Jung-Eun Cho,&nbsp;Jin Ryoun Kim","doi":"10.2174/157488911796958002","DOIUrl":"https://doi.org/10.2174/157488911796958002","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuropathological features comprising amyloid deposits and neuronal losses in brain. In AD, aggregation of a β amyloid peptide (Aβ), produced from proteolytic cleavage of amyloid precursor protein, is believed to be implicated in the pathophysiological cascade leading to neuronal death. Most AD drugs currently available can only alleviate symptoms rather than modify the underlying molecular cause of AD. In this review, we describe and discuss the recent patents issued within the past two years focusing on therapeutic interventions targeting at various Aβ-associated pathological mechanisms of AD. The described therapeutic strategies include 1) reduction of synthesis of Aβ, 2) inhibition of Aβ aggregation, 3) immunotherapeutic/enzymatic clearance of Aβ, 4) targeting other amyloidogenic proteins interacting with Aβ and 5) amelioration of Aβ downstream toxic effects. Important issues to be considered for further improvement of therapeutic efficacy of these approaches are also discussed.</p>","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"6 3","pages":"222-33"},"PeriodicalIF":0.0,"publicationDate":"2011-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/157488911796958002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30072410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological strategies against glucocorticoid-mediated brain damage during chronic disorders.","authors":"Antonio Martocchia,&nbsp;Martina Curto,&nbsp;Lavinia Toussan,&nbsp;Manuela Stefanelli,&nbsp;Paolo Falaschi","doi":"10.2174/157488911796958020","DOIUrl":"https://doi.org/10.2174/157488911796958020","url":null,"abstract":"<p><p>The brain controls coping with aversive situations, modulating the activity of the adaptive systems (the nervous, endocrine and immune systems). In this review, we focus the involvement of the hypothalamus-pituitary-adrenal (HPA) axis in the stress response. In the physiological response, the hypothalamic paraventricular nucleus secretes CRH (corticotrophin releasing hormone) that stimulates pituitary ACTH (adrenocorticotropic hormone), through CRH-receptor type 1 (CRH-R1). In turn, ACTH activates adrenal glands to produce cortisol, acting on type-2 melanocortin receptors (MC2-R). The glucocorticoid negative feedback inhibits the HPA axis activity through the glucocorticoid receptor (GR). The hippocampus plays a central role as an important connection between cortex and hypothalamus, and, together with the suprachiasmatic nucleus (SCN), regulates cortisol rhythm. Peripherally, an important regulator of cortisol metabolism in local tissues is 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), that produces cortisol within the splanchnic bed. The stress response during chronic conditions increases vulnerability to diseases through the activation of adaptive systems, in particular, the HPA axis. Increased levels of allostatic load (a measure of stress with multisystem dysregulation) are associated with the development of functional and cognitive decline, frailty and with mortality in high-functioning older adults. Moreover, HPA axis hyperactivity is a feature that can be present in chronic diseases, affecting endocrine (abdominal obesity, type-2 diabetes mellitus), cardiovascular (atherosclerosis, essential hypertension) and nervous system (dementia, depression), particularly during comorbid conditions. In conclusion, the spectrum of molecules interacting at the different levels of HPA axis is exponentially increasing, ranging from supra-hypothalamic targets to post-receptor mechanisms and it includes agents acting on SCN, CRH-R1 receptor, adrenal steroidogenesis, GR and peripheral/central 11β-HSD1 enzyme. This area of research is rapidly advancing in order to develop therapeutic strategies to counteract HPA axis hyperactivity and to reduce the burden of stress-related disorders. The article presented some promising patents on the strategies against glucocorticoid-mediated brain damage.</p>","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"6 3","pages":"196-204"},"PeriodicalIF":0.0,"publicationDate":"2011-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/157488911796958020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30072411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An update in the management of obesity: the weight of CNS targets.","authors":"Bruno Bariohay,&nbsp;Julien A Roux,&nbsp;Marion S Bonnet,&nbsp;Michel Dallaporta,&nbsp;Jean-Denis Troadec","doi":"10.2174/157488911796958048","DOIUrl":"https://doi.org/10.2174/157488911796958048","url":null,"abstract":"Obesity is one of the most important and disturbing global epidemic that affects humans, with more than 2 billion people overweight and 700 million obese predicted for 2015 by the World Health Organization. Obesity treatment represents then one of the most exciting challenges for the academic researchers and the pharmaceutical industry. But to date, this community failed to develop safe and effective treatments with a good risk/benefit profile. Indeed, most of the drugs previously used as anti-obesity agents have been withdrawn from the market for safety issues, and therapeutic options in form of a medication are currently very limited. This last decade however, new advances in our understanding of central pathways controlling food intake, body weight and energy homeostasis have led to the discovery of new molecular targets that could provide interesting options in the fight against obesity. This review aims to be an overview of the new patents exploiting the anorexigenic properties of the central catabolic pathways or aimed at blocking the orexigenic effects of the anabolic pathways, in the hope to develop new anti-obesity drugs.","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"6 3","pages":"164-80"},"PeriodicalIF":0.0,"publicationDate":"2011-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/157488911796958048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30072413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of diagnostic ultrasound in patient selection for stroke intervention.","authors":"Vijay K Sharma,&nbsp;Prakash R Paliwal,&nbsp;Hock Luen Teoh,&nbsp;N Venketasubramanian,&nbsp;Bernard P L Chan","doi":"10.2174/157488911796957995","DOIUrl":"https://doi.org/10.2174/157488911796957995","url":null,"abstract":"<p><p>Ultrasonography provides a unique diagnostic perspective in cerebrovascular disorders, with extremely high temporal resolution and excellent spatial display of extracranial as well as intracranial arteries. Unlike other imaging modalities, cerebrovascular ultrasound provides real-time information about the blood flow in addition to the hemodynamic changes as a result of various physiological as well as pathological states. The information obtained from cerebrovascular ultrasound has diagnostic, therapeutic as well as prognostic value in various disease states. Transcranial Doppler ultrasonography (TCD) is the only non-invasive examination that provides a reliable evaluation of intracranial blood flow patterns in real-time, adding physiological information to the anatomical information obtained from other neuroimaging modalities. Cerebrovascular ultrasonography is relatively cheap, can be performed bedside, and allows monitoring both in acute emergency settings as well as for prolonged periods with a high temporal resolution. Extended applications of TCD provide important information about the pathophysiology of cerebrovascular ischemia. Advanced applications of cerebrovascular ultrasonography have become an integral part of the armamentarium of stroke neurologists for evaluating stroke mechanisms, plan and monitor treatment and determine prognosis. It has been suggested as an essential component of a comprehensive stroke center. We have reviewed various recent patents in addition to the established applications of cerebrovascular ultrasonography in patient selection for various stroke interventions.</p>","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"6 3","pages":"181-95"},"PeriodicalIF":0.0,"publicationDate":"2011-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/157488911796957995","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30070753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}