Recent patents on CNS drug discovery最新文献_第7页

Polyamine modulation of NMDARs as a mechanism to reduce effects of alcohol dependence. NMDARs的多胺调节作为减少酒精依赖影响的机制。

Recent patents on CNS drug discovery Pub Date : 2012-08-01 DOI: 10.2174/157488912800673128

Susan Barron, Ben Lewis, Kristen Wellmann, Megan Carter, Justin Farook, Josh Ring, Dennis Trent Rogers, Robert Holley, Peter Crooks, John Littleton

{"title":"Polyamine modulation of NMDARs as a mechanism to reduce effects of alcohol dependence.","authors":"Susan Barron, Ben Lewis, Kristen Wellmann, Megan Carter, Justin Farook, Josh Ring, Dennis Trent Rogers, Robert Holley, Peter Crooks, John Littleton","doi":"10.2174/157488912800673128","DOIUrl":"10.2174/157488912800673128","url":null,"abstract":"Relapse and neurodegeneration are two of the major therapeutic targets in alcoholism. Fortuitously, the roles of glutamate/NMDA receptors (NMDARs) in withdrawal, conditioning and neurotoxicity mean that NMDAR inhibitors are potentially valuable for both targets. Preclinical studies further suggest that inhibitory modulators that specifically reduce the co-agonist effects of polyamines on NMDARs are potential non-toxic medications. Using agmatine as a lead compound, over 1000 novel compounds based loosely on this structure were synthesized using feedback from a molecular screen. A novel series of aryliminoguanidines with appropriate NMDAR activity in the molecular screen were discovered (US patent application filed 2007). The most potent and selective aryliminoguanidine, JR 220 [4- (chlorobenzylidenamino)- guanidine hydrochloride], has now been tested in a screening hierarchy for anti-relapse and neuroprotective activity, ranging from cell-based assay, through tissue culture to animal behavior. This hierarchy has been validated using drugs with known, or potential, clinical value at these targets (acamprosate (N-acetyl homotaurine), memantine and topiramate). JR220 was non-toxic and showed excellent activity in every screen with a potency 5-200x that of the FDA-approved anti-relapse agent, acamprosate. This chapter will present a review of the background and rationale for this approach and some of the findings garnered from this approach as well as patents targeting the glutamatergic system especially the NMDAR.","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"7 2","pages":"129-44"},"PeriodicalIF":0.0,"publicationDate":"2012-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554226/pdf/nihms-1031057.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30607806","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: 17

Novel medication targets for the treatment of alcoholism: preclinical studies. 治疗酒精中毒的新药物靶点:临床前研究

Recent patents on CNS drug discovery Pub Date : 2012-08-01 DOI: 10.2174/157488912800673182

Amir H Rezvani, Andrew J Lawrence, Maria P Arolfo, Edward D Levin, David H Overstreet

{"title":"Novel medication targets for the treatment of alcoholism: preclinical studies.","authors":"Amir H Rezvani, Andrew J Lawrence, Maria P Arolfo, Edward D Levin, David H Overstreet","doi":"10.2174/157488912800673182","DOIUrl":"https://doi.org/10.2174/157488912800673182","url":null,"abstract":"Alcoholism is a complex heterogeneous disease and a number of neurotransmitter and neuromodulator systems have been implicated in its manifestation. Consequently, it is unlikely that existing medications such as disulfiram (Antabuse®), naltrexone (ReVia®), acamprosate (Campral®)) can be efficacious in every individual. Thus, the development of novel therapeutic agents with greater selectivity and less unwanted effects for the treatment of this disease is one of the major objectives of alcohol research. This review summarizes the findings of five novel compounds with different neuronal targets for treating alcoholism. These compounds include sazetidine-A, which selectively desensitizes α4β2 nicotinic receptors; carisbamate, a novel anti-epileptic agent; JNJ5234801, a novel anxiolytic agent; GS-455534, a highly selective inhibitor of mitochondrial aldehyde dehydrogenase; and JNJ-39220675, a selective histamine H3 antagonist. Inbred alcohol-preferring rats (iP), Fawn-Hooded (FH) rats, and P rats were used to evaluate the compounds. Naltrexone was used as a positive control in some experiments. All five compounds reduced alcohol consumption and preference. The mechanisms thought to underlie these effects suggest that, in addition to dopaminergic and opioidergic systems, other neuronal systems such as sodium channels (carisbamate), mitochondrial aldehyde dehydrogenase (GS-455534), 5-HT2 receptors (JNJ-5234801), histamine H3 receptors (JNJ-39220675), and α4β2 nicotinic receptors (sazetidine-A) can be involved in alcohol drinking. Further work is necessary to confirm the exact mechanisms of action of each drug and to determine any viable targets for putative treatment of alcohol-use disorders. The article presents some promising patents on novel medication targets for the treatment of alcoholism.","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"7 2","pages":"151-62"},"PeriodicalIF":0.0,"publicationDate":"2012-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/157488912800673182","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30607805","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: 14

Nutraceuticals in psychiatric practice. 精神病学实践中的营养药品。

Recent patents on CNS drug discovery Pub Date : 2012-08-01 DOI: 10.2174/157488912800673119

Matteo Chiappedi, Silvia de Vincenzi, Maurizio Bejor

{"title":"Nutraceuticals in psychiatric practice.","authors":"Matteo Chiappedi, Silvia de Vincenzi, Maurizio Bejor","doi":"10.2174/157488912800673119","DOIUrl":"https://doi.org/10.2174/157488912800673119","url":null,"abstract":"Nutraceuticals can be defined as food components or active principles present in aliments which have positive effects for health and quality of life, including preventing or treating disorders. Herbal and \"natural\" food supplements are increasingly used to treat different psychiatric disorders, often as \"self-prescribed\" therapies. With factors such as chronic illness, poor health, emotional distress, and quality of life influencing the desire for complementary medicine, patients with comorbid medical and psychiatric problems seem likely to turn to this approach. We reviewed the most commonly used herbal and dietary supplements for which a certain efficacy on psychiatric symptoms or disorders has been claimed, checking current Pubmed-indexed literature (the most important being St. John's wort, Omega-3 fatty acids, valerian, Kava, Ginkgo, folate, B vitamins, S-Adenosylmethionine, inositol, alfa-lactoalbumin and passionflower). There is evidence of efficacy for some of these herbs an supplements, proved also by Cochrane's meta-analysis. However many different areas (including efficacy, tolerability, optimal dosing, adequate shelf life, drug and non-pharmacological interactions) need to be thoroughly studied; moreover political decisions need to be scientifically guided in order to best serve psychiatric patients' interests and to prevent using of expensive and sometimes un-useful therapies. This implies that a scientific strategy is needed to rule out any third-part economical interest which could in any way influence therapeutic choices. The article presents some promising patents on nutraceuticals in psychiatric practice.","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"7 2","pages":"163-72"},"PeriodicalIF":0.0,"publicationDate":"2012-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/157488912800673119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30548260","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: 6

Editorial: Pharmacotherapies for the treatment of alcohol abuse and dependence. 社论:治疗酒精滥用和依赖的药物疗法。

Recent patents on CNS drug discovery Pub Date : 2012-08-01 DOI: 10.2174/157488912800673191

Feng C Zhou, Richard L Bell

引用次数: 0

Introduction to the special issue "Pharmacotherapies for the treatment of alcohol abuse and dependence" and a summary of patents targeting other neurotransmitter systems. 介绍特刊“治疗酒精滥用和依赖的药物疗法”和针对其他神经递质系统的专利摘要。

Recent patents on CNS drug discovery Pub Date : 2012-08-01 DOI: 10.2174/157488912800673155

Richard L Bell, Kelle M Franklin, Sheketha R Hauser, Feng C Zhou

{"title":"Introduction to the special issue \"Pharmacotherapies for the treatment of alcohol abuse and dependence\" and a summary of patents targeting other neurotransmitter systems.","authors":"Richard L Bell, Kelle M Franklin, Sheketha R Hauser, Feng C Zhou","doi":"10.2174/157488912800673155","DOIUrl":"10.2174/157488912800673155","url":null,"abstract":"This paper introduces the Special Section: Pharmacotherapies for the Treatment of Alcohol Abuse and Dependence and provides a summary of patents targeting neurotransmitter systems not covered in the other four chapters. The World Health Organization notes that alcoholic-type drinking results in 2.5 million deaths per year, and these deaths occur to a disproportionately greater extent among adolescents and young adults. Developing a pharmacological treatment targeting alcohol abuse and dependence is complicated by (a) the heterogeneous nature of the disease(s), (b) alcohol affecting multiple neurotransmitter and neuromodulator systems, and (c) alcohol affecting multiple organ systems which in turn influence the function of the central nervous system. Presently, the USA Federal Drug Administration has approved three pharmacotherapies for alcoholism: disulfiram, naltrexone, and acamprosate. This chapter provides a summary of the following systems, which are not covered in the accompanying chapters; alcohol and acetaldehyde metabolism, opioid, glycinergic, GABA-A, neurosteroid, dopaminergic, serotonergic, and endocannabinoid, as well as patents targeting these systems for the treatment of alcoholism. Finally, an overview is presented on the use of pharmacogenetics and pharmacogenomics in tailoring treatments for certain subpopulations of alcoholics, which is expected to continue in the future.","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"7 2","pages":"93-112"},"PeriodicalIF":0.0,"publicationDate":"2012-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868366/pdf/nihms526453.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30608318","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

The tachykinergic system as avenues for drug intervention. 快动系统作为药物干预的途径。

Recent patents on CNS drug discovery Pub Date : 2012-08-01 DOI: 10.2174/157488912800673146

Pranela Rameshwar

{"title":"The tachykinergic system as avenues for drug intervention.","authors":"Pranela Rameshwar","doi":"10.2174/157488912800673146","DOIUrl":"https://doi.org/10.2174/157488912800673146","url":null,"abstract":"This review discusses a family of receptors that interact with a family of small peptides that belong to the tachykinin family. The three subtypes of tachykinin receptors follow the following suggested nomenclature: NK1, NK2 and NK3. These receptors belong to the 7-transmembrane, G-protein coupled family. The NK receptor family has been implicated in a wide range of disorders, cancers, inflammation and neural-related diseases. The tachykinin NK receptors and their ligands have been implicated in solid and hematological tumors. Antagonists to NK receptors have been synthesized and some have been tested in preclinical and Phase II clinical studies. However, in order to be effective for treatment, it is imperative to understand the biology of NK receptor family as well as related molecules. One such molecule is HGFIN, also referred as nmb and osteoactivin. HGFIN is particularly relevant since it has been shown to interact with the high affinity ligand of NK1, substance P. This report discusses promising applications for targeting the NK receptors. The discussion proposes potential mechanisms that could occur when substance P interacts with HGFIN as well as the role of HGFIN when antagonists are used to block the NK receptors. This review is relevant for central and peripheral nervous system drug development and cancer targets and also discusses the indications for current patents.","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"7 2","pages":"173-80"},"PeriodicalIF":0.0,"publicationDate":"2012-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/157488912800673146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30548259","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: 6

Cholinergic receptor system as a target for treating alcohol abuse and dependence. 胆碱能受体系统作为治疗酒精滥用和依赖的靶点。

Recent patents on CNS drug discovery Pub Date : 2012-08-01 DOI: 10.2174/157488912800673173

Shafiqur Rahman, Mark A Prendergast

{"title":"Cholinergic receptor system as a target for treating alcohol abuse and dependence.","authors":"Shafiqur Rahman, Mark A Prendergast","doi":"10.2174/157488912800673173","DOIUrl":"https://doi.org/10.2174/157488912800673173","url":null,"abstract":"Alcohol dependence and other alcohol use disorders are major public health problems. Due to the limitations in efficacy with current medications for the management of alcohol abuse and dependence, there is a need for alterantive pharmacotherapies. Emerging preclinical and clinical data indicate that brain nicotinic acetylcholine receptors (nAChRs), a heterogeneous family of ion channels expressed in the mammalian brain, are critical targets for the development of pharmacotherapies for alcohol abuse and dependence. Evidence suggests that the effects of nAChR partial agonists and antagonists have promise for the management of alcohol dependence and other alcohol use disorders. The present review summarizes information on the most recent pharmacotherapies targeting nAChRs, including cytisine, sazetidine A, varenicline, lobeline mecamylamine, PF-4575180 and CP-601932, that are able to treat alcohol dependence. The role of α4β2*, α3β4* and/or other subtypes associated effects in reducing voluntary alcohol consumption or modulate alcohol drinking behavior in animal models and humans are reviewed. Patents discussed include those targeting α4β2* and α7 subtypes as well as cholinesterase inhibitors. Future research indicating the ability of nAChR based compounds to reduce alcohol consumption or modulate alcohol drinking behavior in preclinical and clinical studies, are also discussed.","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"7 2","pages":"145-50"},"PeriodicalIF":0.0,"publicationDate":"2012-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/157488912800673173","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30607804","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: 24

The development of medications for alcohol-use disorders targeting the GABAB receptor system. 针对GABAB受体系统的酒精使用障碍药物的研究进展。

Recent patents on CNS drug discovery Pub Date : 2012-08-01 DOI: 10.2174/157488912800673137

Roberta Agabio, Paola Maccioni, Mauro A M Carai, Gian Luigi Gessa, Wolfgang Froestl, Giancarlo Colombo

{"title":"The development of medications for alcohol-use disorders targeting the GABAB receptor system.","authors":"Roberta Agabio, Paola Maccioni, Mauro A M Carai, Gian Luigi Gessa, Wolfgang Froestl, Giancarlo Colombo","doi":"10.2174/157488912800673137","DOIUrl":"https://doi.org/10.2174/157488912800673137","url":null,"abstract":"The present paper summarizes experimental and clinical data suggesting the therapeutic potential of the prototypic GABAB receptor agonist, baclofen, for the treatment of alcohol-use disorders (AUDs). Numerous studies have reported baclofen-induced suppression of alcohol drinking, relapse-like drinking, and alcohol reinforcing, rewarding, stimulating, and motivational properties in rats and mice. The majority of clinical surveys conducted to date have demonstrated the capacity of baclofen to suppress alcohol consumption, craving for alcohol, and alcohol withdrawal symptomatology in alcohol-dependent patients. More recently, the discovery of a positive allosteric modulatory binding site, together with the synthesis of in vivo effective ligands, provided a new tool for pharmacological manipulations of the GABAB receptor. Accumulating lines of preclinical evidence suggest that positive allosteric modulators of the GABAB receptor (GABAB PAMs), such as GS39783, display a high therapeutic index and retain baclofen's capacity to suppress alcohol consumption and alcohol reinforcing and motivational properties. The present paper also summarizes the most relevant patents on GABAB receptor agonists and GABAB PAMs as possible pharmacotherapies for AUDs.","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"7 2","pages":"113-28"},"PeriodicalIF":0.0,"publicationDate":"2012-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/157488912800673137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30607807","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: 19

Therapeutic perspectives in Alzheimer's disease. 阿尔茨海默病的治疗前景。

Recent patents on CNS drug discovery Pub Date : 2012-07-25 DOI: 10.2174/1574889810601010119

J. Tschäpe, T. Hartmann

{"title":"Therapeutic perspectives in Alzheimer's disease.","authors":"J. Tschäpe, T. Hartmann","doi":"10.2174/1574889810601010119","DOIUrl":"https://doi.org/10.2174/1574889810601010119","url":null,"abstract":"It is now almost a century ago that Alois Alzheimer first presented his results in public. Main characteristics of Alzheimer's disease (AD) are massive cerebral accumulation of amyloid, composed of fibrillary aggregates of the Amyloid beta peptide (Abeta) and intracellular accumulation of abnormally phosphorylated tau protein associated with widespread neurodegeneration. The clinical picture is characterized by progressive and irreversible dementia, which is eventually fatal. To date, there is no cure for this severe disease affecting more than of 30 million individuals worldwide. In the last decades, the treatment of Alzheimer patients was mainly focusing on symptomatical strategies. Based on the augmented knowledge about the mechanisms underlying the pathology of AD, particularly the molecular causes and consequences of AD, different therapeutic approaches arose and recently, treatment with Statins, NSAIDs and Abeta vaccines reached the level of clinical trials, showing some indication of efficacy already. According to actual evaluations, these approaches have realistic chances to become established as therapeutic routine in AD within the next 10 years. We will review here some of the most promising novel approaches to cure and prevent rather than to treat the symptoms of AD.","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"1 1 1","pages":"119-27"},"PeriodicalIF":0.0,"publicationDate":"2012-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67992962","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: 27

Recent patents on CNS drug discovery Pub Date : 2012-04-01 DOI: 10.2174/157488912798842269

Simone Tambaro, Marco Bortolato

{"title":"Cannabinoid-related agents in the treatment of anxiety disorders: current knowledge and future perspectives.","authors":"Simone Tambaro, Marco Bortolato","doi":"10.2174/157488912798842269","DOIUrl":"10.2174/157488912798842269","url":null,"abstract":"Rich evidence has shown that cannabis products exert a broad gamut of effects on emotional regulation. The main psychoactive ingredient of hemp, Δ9-tetrahydrocannabinol (THC), and its synthetic cannabinoid analogs have been reported to either attenuate or exacerbate anxiety and fear-related behaviors in humans and experimental animals. The heterogeneity of cannabis-induced psychological outcomes reflects a complex network of molecular interactions between the key neurobiological substrates of anxiety and fear and the endogenous cannabinoid system, mainly consisting of the arachidonic acid derivatives anandamide and 2-arachidonoylglycerol (2-AG) and two receptors, respectively termed CB1 and CB2. The high degree of interindividual variability in the responses to cannabis is contributed by a wide spectrum of factors, including genetic and environmental determinants, as well as differences in the relative concentrations of THC and other alkaloids (such as cannabidiol) within the plant itself. The present article reviews the currently available knowledge on the herbal, synthetic and endogenous cannabinoids with respect to the modulation of anxiety responses, and highlights the challenges that should be overcome to harness the therapeutic potential of some of these compounds, all the while limiting the side effects associated with cannabis consumption. In addition the article presents some promising patents on cannabinoid-related agents.","PeriodicalId":87737,"journal":{"name":"Recent patents on CNS drug discovery","volume":"7 1","pages":"25-40"},"PeriodicalIF":0.0,"publicationDate":"2012-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3691841/pdf/nihms-482368.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30415229","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