Current drug targets. CNS and neurological disorders最新文献

Cannabinoids. 大麻类。

Current drug targets. CNS and neurological disorders Pub Date : 2020-09-01 DOI: 10.31887/dcns.22.3

F. Grotenhermen

{"title":"Cannabinoids.","authors":"F. Grotenhermen","doi":"10.31887/dcns.22.3","DOIUrl":"https://doi.org/10.31887/dcns.22.3","url":null,"abstract":"Since the discovery of an endogenous cannabinoid system, research into the pharmacology and therapeutic potential of cannabinoids has steadily increased. Two subtypes of G-protein coupled cannabinoid receptors, CB(1) and CB(1), have been cloned and several putative endogenous ligands (endocannabinoids) have been detected during the past 15 years. The main endocannabinoids are arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol (2-AG), derivatives of arachidonic acid, that are produced \"on demand\" by cleavage of membrane lipid precursors. Besides phytocannabinoids of the cannabis plant, modulators of the cannabinoid system comprise synthetic agonists and antagonists at the CB receptors and inhibitors of endocannabinoid degradation. Cannabinoid receptors are distributed in the central nervous system and many peripheral tissues, including immune system, reproductive and gastrointestinal tracts, sympathetic ganglia, endocrine glands, arteries, lung and heart. There is evidence for some non-receptor dependent mechanisms of cannabinoids and for endocannabinoid effects mediated by vanilloid receptors. Properties of CB receptor agonists that are of therapeutic interest include analgesia, muscle relaxation, immunosuppression, anti-inflammation, antiallergic effects, improvement of mood, stimulation of appetite, antiemesis, lowering of intraocular pressure, bronchodilation, neuroprotection and antineoplastic effects. The current main focus of clinical research is their efficacy in chronic pain and neurological disorders. CB receptor antagonists are under investigation for medical use in obesity and nicotine addiction. Additional potential was proposed for the treatment of alcohol and heroine dependency, schizophrenia, conditions with lowered blood pressure, Parkinson's disease and memory impairment in Alzheimer's disease.","PeriodicalId":11063,"journal":{"name":"Current drug targets. CNS and neurological disorders","volume":"33 1","pages":"507-30"},"PeriodicalIF":0.0,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74951798","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: 0

Cannabinoids: between neuroprotection and neurotoxicity. 大麻素:介于神经保护和神经毒性之间。

Current drug targets. CNS and neurological disorders Pub Date : 2005-12-01 DOI: 10.2174/156800705774933005

Yosef Sarne, Raphael Mechoulam

引用次数: 110

Partial QSAR analysis of some selected natural inhibitors of FAAH suggests a working hypothesis for the development of endocannabinoid-based drugs. 一些选定的FAAH天然抑制剂的部分QSAR分析为内源性大麻素类药物的开发提供了一个可行的假设。

Current drug targets. CNS and neurological disorders Pub Date : 2005-12-01 DOI: 10.2174/156800705774933096

Enrico Dainese, Valeria Gasperi, Mauro Maccarrone

{"title":"Partial QSAR analysis of some selected natural inhibitors of FAAH suggests a working hypothesis for the development of endocannabinoid-based drugs.","authors":"Enrico Dainese, Valeria Gasperi, Mauro Maccarrone","doi":"10.2174/156800705774933096","DOIUrl":"https://doi.org/10.2174/156800705774933096","url":null,"abstract":"The endogenous cannabinoids (endocannabinoids) are bioactive signaling molecules, that show diverse cellular and physiological effects and play various roles in the central nervous system, as well as in the periphery. The discovery of N-arachidonoylethanolamine (anandamide, AEA) and of the enzyme that terminates its signaling, i. e. fatty acid amide hydrolase (FAAH), has inspired pharmacological strategies to augment endocannabinoid tone and biological activity through inhibition of FAAH. Here we discuss the role of natural endocannabinoid derivatives, like the hydroxy-anandamides (OH-AEAs) generated from AEA via lipoxygenase activity, as powerful inhibitors of FAAH. We propose that these compounds, by reversibly inhibiting FAAH, may control in vivo the endocannabinoid tone. We consider the theoretical structural properties of OH-AEAs and other natural inhibitors of FAAH, based on the calculation of theoretical molecular descriptors commonly used in Quantitative Structure Activity Relationship (QSAR) studies. The QSAR properties of OH-AEAs and congeners suggest that they could act at different specific sites of FAAH, thus confirming their potential value as templates for the development of next-generation therapeutics.","PeriodicalId":11063,"journal":{"name":"Current drug targets. CNS and neurological disorders","volume":"4 6","pages":"709-14"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/156800705774933096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25768684","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: 10

The endocannabinoid system in the brain: from biology to therapy. 大脑中的内源性大麻素系统:从生物学到治疗。

Current drug targets. CNS and neurological disorders Pub Date : 2005-12-01 DOI: 10.2174/156800705774933078

Mauro Maccarrone

引用次数: 3

From cannabis to endocannabinoids in multiple sclerosis: a paradigm of central nervous system autoimmune diseases. 从大麻到内源性大麻素在多发性硬化症:中枢神经系统自身免疫性疾病的范例。

Current drug targets. CNS and neurological disorders Pub Date : 2005-12-01 DOI: 10.2174/156800705774933087

Anna Maria Malfitano, Giuseppe Matarese, Maurizio Bifulco

{"title":"From cannabis to endocannabinoids in multiple sclerosis: a paradigm of central nervous system autoimmune diseases.","authors":"Anna Maria Malfitano, Giuseppe Matarese, Maurizio Bifulco","doi":"10.2174/156800705774933087","DOIUrl":"https://doi.org/10.2174/156800705774933087","url":null,"abstract":"An increasing body of evidence suggests that cannabinoids have beneficial effects on the symptoms of multiple sclerosis, including spasticity and pain. Endogenous molecules with cannabinoid-like activity, such as the \"endocannabinoids\", have been shown to mimic the anti-inflammatory properties of cannabinoids through the cannabinoid receptors. Several studies suggest that cannabinoids and endocannabinoids may have a key role in the pathogenesis and therapy of multiple sclerosis. Indeed, they can down regulate the production of pathogenic T helper 1-associated cytokines enhancing the production of T helper 2-associated protective cytokines. A shift towards T helper 2 has been associated with therapeutic benefit in multiple sclerosis. In addition, cannabinoids exert a neuromodulatory effect on neurotransmitters and hormones involved in the neurodegenerative phase of the disease. In vivo studies using mice with experimental allergic encephalomyelitis, an animal model of multiple sclerosis, suggest that the increase of the circulating levels of endocannabinoids might have a therapeutic effect, and that agonists of endocannabinoids with low psychoactive effects could open new strategies for the treatment of multiple sclerosis.","PeriodicalId":11063,"journal":{"name":"Current drug targets. CNS and neurological disorders","volume":"4 6","pages":"667-75"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/156800705774933087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25768680","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: 18

Endocannabinoids in neuroimmunology and stress. 内源性大麻素在神经免疫学和应激中的作用。

Current drug targets. CNS and neurological disorders Pub Date : 2005-12-01 DOI: 10.2174/156800705774933023

E J Carrier, S Patel, C J Hillard

{"title":"Endocannabinoids in neuroimmunology and stress.","authors":"E J Carrier, S Patel, C J Hillard","doi":"10.2174/156800705774933023","DOIUrl":"https://doi.org/10.2174/156800705774933023","url":null,"abstract":"Two topics are presented in this review. In the first section, we review data regarding the effects of the endocannabinoids (eCBs) and cannabinoid receptors on neuroimmune function. The function of eCBs in the interaction between the immune system and the central nervous system (CNS) is of particular interest, since the CNS itself is a rich source of eCBs while being exquisitely sensitive to inflammation. There are several sites at which cannabinoids can influence neuroinflammation. Microglial cells express both CB receptors and make eCBs. Activation of CB receptors on these cells seems to promote migration and proliferation but to reduce activation to macrophages. In several neurodegenerative diseases, up-regulation of microglial CB2 receptors have been observed. It is our hypothesis that microglial CB receptor activity is anti-inflammatory and could be exploited to manipulate neuroinflammatory processes with a minimum of unwanted effects. The second topic discussed suggests that the eCB/CB1 receptor pair is involved in the responses of animals to acute, repeated and variable stress. The roles of this pair are complex and dependent upon previous stress, among other things. Dysfunctional responding to stress is a component of several human neuropsychiatric disorders, including anxiety and panic disorders, post-traumatic stress disorders, premenstrual dysphoria and quite possibly, drug abuse. While it is too early to say with certainty, it is very possible that either inhibition or potentiation of endocannabinoid signaling will be an efficacious novel therapeutic approach to more than one human psychiatric disease.","PeriodicalId":11063,"journal":{"name":"Current drug targets. CNS and neurological disorders","volume":"4 6","pages":"657-65"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/156800705774933023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25768679","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: 71

Endocannabinoids and drug dependence. 内源性大麻素和药物依赖。

Current drug targets. CNS and neurological disorders Pub Date : 2005-12-01 DOI: 10.2174/156800705774933014

Daniela Parolaro, Daniela Viganò, Tiziana Rubino

{"title":"Endocannabinoids and drug dependence.","authors":"Daniela Parolaro, Daniela Viganò, Tiziana Rubino","doi":"10.2174/156800705774933014","DOIUrl":"https://doi.org/10.2174/156800705774933014","url":null,"abstract":"Drug dependence is a chronically relapsing disorder, manifested as an intense desire for the drug, with impaired ability to control the urges to take the drug, even at the expense of serious adverse consequences. These behavioral abnormalities develop gradually during repeated exposure to a drug of abuse, and can persist for months or years after discontinuation of use, suggesting that this addiction can be considered a form of drug-induced neural plasticity. Many neurotransmitters, including gamma-aminobutyric acid (GABA), glutamate, acetylcholine, dopamine, serotonin and endogenous opioid peptides, have been implicated in the effects of the various drugs of abuse. Dopamine has been consistently associated with the reinforcing effects of most of them. There is, in addition, a growing body of evidence that the endogenous cannabinoid system might participate in the motivational and dopamine-releasing effects of several drugs of abuse. This review will discuss the latest advances on the mechanisms of cannabinoid dependence and the possible role of the endocannabinoid system in the treatment of addiction, not only to marijuana but also to the other common illicit drugs.","PeriodicalId":11063,"journal":{"name":"Current drug targets. CNS and neurological disorders","volume":"4 6","pages":"643-55"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/156800705774933014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25768678","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: 39

Therapeutic perspectives of inhibitors of endocannabinoid degradation. 内源性大麻素降解抑制剂的治疗前景。

Current drug targets. CNS and neurological disorders Pub Date : 2005-12-01 DOI: 10.2174/156800705774933032

Silvia Ortega-Gutiérrez

{"title":"Therapeutic perspectives of inhibitors of endocannabinoid degradation.","authors":"Silvia Ortega-Gutiérrez","doi":"10.2174/156800705774933032","DOIUrl":"https://doi.org/10.2174/156800705774933032","url":null,"abstract":"The study of the cannabinoids can be established in the middle sixties with the elucidation of the structure of the active principle of Cannabis sativa plant, the delta9-tetrahydrocannabinol. However, the existence of an endogenous cannabinoid system (ECS) has not been unequivocally accepted until recently. The last two decades have witnessed an impressive advance in the knowledge about cannabinoids, their chemistry, the enzymes involved in their metabolism, and their physiological and pathological roles. In particular, we have made progress in modifying the activity of the ECS with selective compounds, validating the ECS as a new therapeutic target. Endocannabinoids play a role in physiological and pathological processes, and their levels are affected in several disorders. Therefore, it should be possible to ameliorate these pathologies by correcting their altered levels. This review focuses on the current therapeutic opportunities of endocannabinoid-directed drugs, and pays special attention to the therapeutic possibilities underlying the inhibition of the endocannabinoid inactivation. The strategy of manipulating the ECS might open new avenues in the development of therapeutic approaches for a number of disorders, both central and peripheral, that lack as yet effective treatments.","PeriodicalId":11063,"journal":{"name":"Current drug targets. CNS and neurological disorders","volume":"4 6","pages":"697-707"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/156800705774933032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25768683","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: 20

Endocannabinoid metabolic pathways and enzymes. 内源性大麻素代谢途径和酶。

Current drug targets. CNS and neurological disorders Pub Date : 2005-12-01 DOI: 10.2174/156800705774933104

Alessia Ligresti, Maria Grazia Cascio, Vincenzo Di Marzo

引用次数: 78

Endocannabinoids in the central nervous system: from neuronal networks to behavior. 中枢神经系统中的内源性大麻素:从神经网络到行为。

Current drug targets. CNS and neurological disorders Pub Date : 2005-12-01 DOI: 10.2174/156800705774933069

Ester Fride

{"title":"Endocannabinoids in the central nervous system: from neuronal networks to behavior.","authors":"Ester Fride","doi":"10.2174/156800705774933069","DOIUrl":"https://doi.org/10.2174/156800705774933069","url":null,"abstract":"Retrograde synaptic signaling influences both short-term and long-term plasticity of the brain, in both excitatory and inhibitory synapses. During the last few years it has become apparent that the endogenous ligands for the cannabinoid CB1 receptor, the \"endocannabinoids\", fulfill an essential role in the brain as retrograde synaptic messengers, in a number of structures including the hippocampus, cerebellum and the limbic and mesocortical systems. This seminal discovery provides a cellular basis for the well known ubiquitous role of the endocannabinoids and their receptors (together, the \"ECBR\" system) in virtually all brain functions studied. This review will relate the anatomical distribution of the endocannabinoids and their CB1 receptors to functions of the ECBR system, as much as possible in light of the endocannabinoids as retrograde synaptic messengers. Functional implications of the high rates of co-localization with cholecystokinin (CCK), will also be considered. The most obvious function to be profoundly affected by the retrograde synaptic role of the endocannabinoids is memory. However, additional functions and dysfunctions such as reward and addiction, motor coordination, pain perception, feeding and appetite, coping with stress, schizophrenia and epilepsy will also be reviewed. Finally, the widespread presence of the ECBR system in the brain also lends a scientific basis for the development of cannabinoid-based medicines. The same ubiquity of the ECBR system however, should also be taken into consideration with respect to possible adverse side effects and addictive potential of such pharmaceutical developments.","PeriodicalId":11063,"journal":{"name":"Current drug targets. CNS and neurological disorders","volume":"4 6","pages":"633-42"},"PeriodicalIF":0.0,"publicationDate":"2005-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/156800705774933069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25768677","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: 77