Recent patents on CNS drug discovery最新文献_第9页

Neurogenic ejaculatory disorders: focus on current and future treatments. 神经源性射精障碍:关注当前和未来的治疗。

Recent patents on CNS drug discovery Pub Date : 2011-09-01 DOI: 10.2174/157488911796958011

Rocco S Calabrò, Giovanni Polimeni, Rosella Ciurleo, Carmela Casella, Placido Bramanti

{"title":"Neurogenic ejaculatory disorders: focus on current and future treatments.","authors":"Rocco S Calabrò, Giovanni Polimeni, Rosella Ciurleo, Carmela Casella, Placido Bramanti","doi":"10.2174/157488911796958011","DOIUrl":"https://doi.org/10.2174/157488911796958011","url":null,"abstract":"Ejaculation is a complex and still poorly understood neurological mechanism, at both spinal and cerebral levels as it is closely associated with orgasm. Physiologically, ejaculation is defined as the expulsion of seminal fluid from the urethral meatus and consists of two phases, namely emission and expulsion. Ejaculation is mediated by a spinal control center, referred to as a spinal pattern generator that coordinates sympathetic, parasympathetic and motor (somatic) outflows, integrating the latter with the inputs from the supraspinal sites in brainstem, hypothalamus and preoptic area. Premature ejaculation (PE) is the most common sexual dysfunction among young men, and it has been considered mostly psychogenic in origin, although it can be associated to diverse urological and neurological diseases. On the contrary, retrograde ejaculation and anejaculation are predominantly related to organic causes, particularly to neurogenic ones. Since ejaculation is mostly a spinal reflex, it is comprehensible that ejaculatory disorders are more frequent in spinal cord injury than in other neurological disorders. Over the past decades, research has focused on PE, and evidence from clinical studies showed a beneficial effect of antidepressants for the treatment of men with PE. Other ejaculatory disorders, especially painful ejaculation, have been less investigated and the proper therapy is still controversial. Aim of this review is to provide a comprehensive description of both currently available treatments and most promising future therapies, including assigned patents, for the neurogenic ejaculatory disorders.","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"6 3","pages":"205-21"},"PeriodicalIF":0.0,"publicationDate":"2011-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/157488911796958011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30072412","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}

引用次数: 17

Patented in vitro blood-brain barrier models in CNS drug discovery. 获得专利的体外血脑屏障模型用于中枢神经系统药物发现。

Recent patents on CNS drug discovery Pub Date : 2011-05-01 DOI: 10.2174/157488911795933910

Andrea Tóth, Szilvia Veszelka, Shinsuke Nakagawa, Masami Niwa, Mária A Deli

{"title":"Patented in vitro blood-brain barrier models in CNS drug discovery.","authors":"Andrea Tóth, Szilvia Veszelka, Shinsuke Nakagawa, Masami Niwa, Mária A Deli","doi":"10.2174/157488911795933910","DOIUrl":"https://doi.org/10.2174/157488911795933910","url":null,"abstract":"The blood-brain barrier (BBB) is a regulatory interface between the circulation and the central nervous system (CNS). Therapy of neurological diseases is limited due to restricted penetration of pharmacons across the BBB. Models for screening the brain penetration of drug candidates are needed early in drug discovery. Culture-based models are useful tools for both basic research on BBB, and testing the permeability of new therapeutical molecules. This review focuses on patented in vitro BBB models and their potential application in CNS drug discovery. Cell culture models using primary and immortalized brain endothelial cells of non-human and human origin, in co-culture or mono-culture setting, in static or dynamic conditions are discussed, as well as methods to induce BBB properties in such in vitro models. The aim of these models is to reproduce as many aspects as possible of the in vivo BBB. All models should show some elements of general endothelial and specific BBB properties, like physiologically realistic cell architecture, restrictive paracellular pathway, and functional expression of transport mechanisms. Though no \"ideal in vitro BBB model\" has been constructed yet, the currently available models provide valuable information on BBB permeability and are useful tools in CNS drug discovery.","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"6 2","pages":"107-18"},"PeriodicalIF":0.0,"publicationDate":"2011-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/157488911795933910","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40085413","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}

引用次数: 67

Metoclopramide as an analgesic in severe migraine attacks: an open, single-blind, parallel control study. 甲氧氯普胺作为严重偏头痛发作的镇痛药:一项开放、单盲、平行对照研究。

Recent patents on CNS drug discovery Pub Date : 2011-05-01 DOI: 10.2174/157488911795933947

G Salazar, M Fragoso, L Vergez, P Sergio, D Cuello

{"title":"Metoclopramide as an analgesic in severe migraine attacks: an open, single-blind, parallel control study.","authors":"G Salazar, M Fragoso, L Vergez, P Sergio, D Cuello","doi":"10.2174/157488911795933947","DOIUrl":"https://doi.org/10.2174/157488911795933947","url":null,"abstract":"Metoclopramide is a well-known anti-emetic drug with central and peripheral pharmacological effects. Some authors have reported metoclopramide as an adjunct therapy to other analgesics in patients with migraine attacks. Treatment of migraine headache using a mix of metoclopramide and an NSAID has been patented (European Patent EP1014961) as well as a short series showing great efficacy and tolerability of metoclopramide in patients wtih migraine attacks. We decided to conduct an open, single-blind, parallel control study in the emergency department to evaluate the efficacy and tolerability of metoclopramide in patients with severe migraine attacks. 93 consecutive patients with severe migraine attacks were randomized into two groups (groups A and B). Patients in group A received 10mg of intravenous metoclopramide and patients in group B received 1 g of intravenous paracetamol. Patients were evaluated 5 minutes before (baseline), 15, 30, 60 and 120 minutes after drug delivery, and before being discharged from the emergency department They were then contacted by phone 48 hours after being discharged from the hospital (phone questionnaire). Patients treated with either metoclopramide or paracetamol showed a significant reduction in the intensity of pain at the 120 minute time point, with an 86% and 82% improvement respectively. However, patients treated with metoclopramide showed a more rapid improvement at the 15 and 30 minute evaluations. Patients with severe migraine attacks treated with metoclopramide as monotherapy showed a significant improvement in terms of pain relief and a faster improvement in pain intensity compared to those treated with paracetamol. Metoclopramide and other dopamine antagonistic drugs should be considered a therapeutic option in severe migraine headache attacks.","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"6 2","pages":"141-5"},"PeriodicalIF":0.0,"publicationDate":"2011-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40085416","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}

引用次数: 13

Analgesic and antineuropathic drugs acting through central cholinergic mechanisms. 通过中枢胆碱能机制发挥作用的镇痛和抗神经病学药物。

Recent patents on CNS drug discovery Pub Date : 2011-05-01 DOI: 10.2174/157488911795933901

Alessandro Bartolini, Lorenzo Di Cesare Mannelli, Carla Ghelardini

{"title":"Analgesic and antineuropathic drugs acting through central cholinergic mechanisms.","authors":"Alessandro Bartolini, Lorenzo Di Cesare Mannelli, Carla Ghelardini","doi":"10.2174/157488911795933901","DOIUrl":"10.2174/157488911795933901","url":null,"abstract":"The role of muscarinic and nicotinic cholinergic receptors in analgesia and neuropathic pain relief is relatively unknown. This review describes how such drugs induce analgesia or alleviate neuropathic pain by acting on the central cholinergic system. Several pharmacological strategies are discussed which increase synthesis and release of acetylcholine (ACh) from cholinergic neurons. The effects of their acute and chronic administration are described. The pharmacological strategies which facilitate the physiological functions of the cholinergic system without altering the normal modulation of cholinergic signals are highlighted. It is proposed that full agonists of muscarinic or nicotinic receptors should be avoided. Their activation is too intense and un-physiological because neuronal signals are distorted when these receptors are constantly activated. Good results can be achieved by using agents that are able to a) increase ACh synthesis, b) partially inhibit cholinesterase activity c) selectively block the autoreceptor or heteroreceptor feedback mechanisms. Activation of M(1) subtype muscarinic receptors induces analgesia. Chronic stimulation of nicotinic (N(1)) receptors has neuronal protective effects. Recent experimental results indicate a relationship between repeated cholinergic stimulation and neurotrophic activation of the glial derived neurotrophic factor (GDNF) family. At least 9 patents covering novel chemicals for cholinergic system modulation and pain control are discussed.","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"6 2","pages":"119-40"},"PeriodicalIF":0.0,"publicationDate":"2011-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40085786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Promising medications for cocaine dependence treatment. 有望治疗可卡因依赖的药物。

Recent patents on CNS drug discovery Pub Date : 2011-05-01 DOI: 10.2174/157488911795933893

Lorenzo Somaini, Claudia Donnini, Maria A Raggi, Mario Amore, Roberto Ciccocioppo, Maria A Saracino, Marsida Kalluppi, Marco Malagoli, Maria L Gerra, Gilberto Gerra

{"title":"Promising medications for cocaine dependence treatment.","authors":"Lorenzo Somaini, Claudia Donnini, Maria A Raggi, Mario Amore, Roberto Ciccocioppo, Maria A Saracino, Marsida Kalluppi, Marco Malagoli, Maria L Gerra, Gilberto Gerra","doi":"10.2174/157488911795933893","DOIUrl":"https://doi.org/10.2174/157488911795933893","url":null,"abstract":"Cocaine dependence is characterized by compulsive drug seeking and high vulnerability to relapse. Overall, cocaine remains one of the most used illicit drugs in the world. Given the difficulty of achieving sustained recovery, pharmacotherapy of cocaine addiction remains one of the most important clinical challenges. Recent advances in neurobiology, brain imaging and clinical trials suggest that certain medications show promise in the treatment of cocaine addiction. The pharmacotherapeutic approaches for cocaine dependence include medications able to target specific subtypes of dopamine receptors, affect different neurotransmitter systems (i.e. noradrenergic, serotonergic, cholinergic, glutamatergic, GABAergic and opioidergic pathways), and modulate neurological processes. The systematic reviews concerning the pharmacological treatment of cocaine dependence appear to indicate controversial findings and inconclusive results. The aim of future studies should be to identify the effective medications matching the specific needs of patients with specific characteristics, abandoning the strategies extended to the entire population of cocaine dependent patients. In the present review we summarize the current pharmacotherapeutic approaches to the treatment of cocaine dependence with a focus on the new patents.","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"6 2","pages":"146-60"},"PeriodicalIF":0.0,"publicationDate":"2011-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40098690","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}

引用次数: 28

BACE inhibitors as potential drugs for the treatment of Alzheimer's disease: focus on bioactivity. BACE抑制剂作为治疗阿尔茨海默病的潜在药物:关注生物活性。

Recent patents on CNS drug discovery Pub Date : 2011-05-01 DOI: 10.2174/157488911795933938

Genevieve Evin, Guillaume Lessene, Simon Wilkins

引用次数: 55

Potential drugs and methods for preventing or delaying the progression of Huntington's disease. 预防或延缓亨廷顿氏病进展的潜在药物和方法。

Recent patents on CNS drug discovery Pub Date : 2011-05-01 DOI: 10.2174/157488911795933884

Youssef Sari

引用次数: 0

Recent developments in therapeutic approaches for lysosomal storage diseases. 溶酶体贮积病治疗方法的最新进展。

Recent patents on CNS drug discovery Pub Date : 2011-01-01 DOI: 10.2174/157488911794079127

Lorena Urbanelli, Alessandro Magini, Alice Polchi, Mario Polidoro, Carla Emiliani

{"title":"Recent developments in therapeutic approaches for lysosomal storage diseases.","authors":"Lorena Urbanelli, Alessandro Magini, Alice Polchi, Mario Polidoro, Carla Emiliani","doi":"10.2174/157488911794079127","DOIUrl":"https://doi.org/10.2174/157488911794079127","url":null,"abstract":"Genetic mutations that cause specific lysosomal protein deficiencies account for more than 45 Lysosomal Storage Diseases (LSDs), mostly pre-adult disorders which are associated with neurological symptoms and mental retardation. Interestingly, such diseases are often characterized by intracellular deposition and protein aggregation, events also found in age-related neurodegenerative diseases. During the past twenty years, different approaches have been introduced for the treatment of these disorders, several of which are now in routine clinical use or clinical trials. Among them, enzyme replacement therapy (ERT) represented a major progress. However, the usefulness of ERT is limited due to the fact that enzyme distribution is insufficient and treatment costs are very high. A further novel therapeutic option for LSDs is based on the use of small molecules, that can either inhibit a key enzyme which is responsible for substrate synthesis (substrate reduction) or act as a chaperone to increase the residual activity of the lysosomal enzyme (pharmacological chaperones). In addition, recently various gene therapy approaches have been developed, mostly based on adeno-associated and lentiviral vectors, and strategies based on stem cells administration are beginning their route. This review provides an update of the status of research on LSDs therapeutic approaches, including recent patents in the field.","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"6 1","pages":"1-19"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/157488911794079127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29465745","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}

引用次数: 25

Future targeted disease modifying drugs for Alzheimer's disease. 未来针对阿尔茨海默病的疾病修饰药物。

Recent patents on CNS drug discovery Pub Date : 2011-01-01 DOI: 10.2174/157488911794079073

Sandip K Dash

引用次数: 1

Current and future therapies of erectile dysfunction in neurological disorders. 神经系统疾病中勃起功能障碍的当前和未来治疗。

Recent patents on CNS drug discovery Pub Date : 2011-01-01 DOI: 10.2174/157488911794079082

Rocco S Calabrò, Giovanni Polimeni, Placido Bramanti

引用次数: 17