CNS drug reviews最新文献

{"title":"ACKNOWLEDGMENT OF REVIEWERS","authors":"","doi":"10.1111/j.1527-3458.2007.00028.x","DOIUrl":"https://doi.org/10.1111/j.1527-3458.2007.00028.x","url":null,"abstract":"","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"13 4","pages":"507"},"PeriodicalIF":0.0,"publicationDate":"2007-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.00028.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137638836","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}

{"title":"Cortagine: Behavioral and Autonomic Function of the Selective CRF Receptor Subtype 1 Agonist","authors":"Catherine Borna Farrokhi,&nbsp;Philip Tovote,&nbsp;Robert J. Blanchard,&nbsp;D. Caroline Blanchard,&nbsp;Yoav Litvin,&nbsp;Joachim Spiess","doi":"10.1111/j.1527-3458.2007.00027.x","DOIUrl":"10.1111/j.1527-3458.2007.00027.x","url":null,"abstract":"<p>Corticotropin-releasing factor (CRF) is a neuropeptide and mediating component of neuroendocrine, autonomic, and behavioral processes associated with the stress response. The two receptor subtypes identified in the mammalian brain, CRF receptor subtype 1 (CRF1) and CRF2, are suggested to differentially modulate these processes. Manipulation of these receptors with selective CRF compounds and transgenic models has revealed, in most studies, a clear potentiation of the stress response through central activation of CRF1. However, pharmacological activation of CRF restricted to CRF1 has been limited by the availability of selective peptidic compounds. Recently, a highly selective CRF1 agonist, cortagine, has been developed. It was synthesized from chimeric intermediate sequences of ovine CRF, sauvagine, and human/rat CRF into a highly soluble peptide with strong affinity for CRF1 (IC₅₀ &lt; 5 nM) and a very low binding preference for CRF2 (IC₅₀ &gt; 500 nM). Affinity for the CRF binding protein (IC₅₀ &gt; 1,000nM) can be abolished by the addition of a glutamate residue on position 21 of the cortagine peptide sequence. Cortagine has recently been tested in a variety of preclinical models of behavior including the elevated-plus-maze (EPM), forced swim test (FST), homecage, and rat exposure test (RET). Preliminary characterization in the EPM and FST suggested that this compound elicits anxiogenic and antidepressant-like effects, respectively. Additional testing in the homecage and RET, which targets various elements of behavior, directs to a more potent anxiogenic profile of cortagine. In this review, we discuss the behavioral findings and the tests used to measure these effects. Finally, we also discuss preliminary findings of autonomic activation obtained by central injection of cortagine that support CRF1 involvement in the modulation of heart rate and heart rate variability.</p>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"13 4","pages":"423-443"},"PeriodicalIF":0.0,"publicationDate":"2007-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.00027.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27116734","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}

{"title":"Guanfacine and Guanfacine Extended Release: Treatment for ADHD and Related Disorders","authors":"David J. Posey,&nbsp;Christopher J. McDougle","doi":"10.1111/j.1527-3458.2007.00026.x","DOIUrl":"10.1111/j.1527-3458.2007.00026.x","url":null,"abstract":"<p>Guanfacine, an α_2A adrenoceptor agonist, is U.S. Food and Drug Administration (FDA)–approved for the treatment of hypertension in adolescents and adults. It also has been used \"off-label\" for several years in children as a possible treatment for attention-deficit/hyperactivity disorder (ADHD) and pervasive developmental disorders (PDDs). Small placebo-controlled trials support the use of guanfacine for the treatment of ADHD. There is more limited research on the use of guanfacine in treating hyperactivity occurring in children diagnosed with PDD. Recently, guanfacine extended release (GXR), a once-daily formulation has been manufactured and studied in phase III clinical trials. Based on preliminary scientific presentations, it also appears to be efficacious in improving ADHD in children. The most common adverse effects associated with guanfacine and GXR treatment is sedation. Adverse cardiovascular effects are uncommon, although modest reductions in blood pressure and heart rate are common. If GXR is FDA-approved, it would be the first α_2A adrenoceptor agonist marketed for ADHD.</p>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"13 4","pages":"465-474"},"PeriodicalIF":0.0,"publicationDate":"2007-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.00026.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27117130","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}

{"title":"AUTHOR INDEX FOR VOLUME 13","authors":"","doi":"10.1111/j.1527-3458.2007.auindex_1.x","DOIUrl":"https://doi.org/10.1111/j.1527-3458.2007.auindex_1.x","url":null,"abstract":"","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"13 4","pages":"502-503"},"PeriodicalIF":0.0,"publicationDate":"2007-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.auindex_1.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137638835","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}

{"title":"Pharmacology of the β-Carboline FG-7142, a Partial Inverse Agonist at the Benzodiazepine Allosteric Site of the GABAA Receptor: Neurochemical, Neurophysiological, and Behavioral Effects","authors":"Andrew K. Evans,&nbsp;Christopher A. Lowry","doi":"10.1111/j.1527-3458.2007.00025.x","DOIUrl":"10.1111/j.1527-3458.2007.00025.x","url":null,"abstract":"<p>Given the well-established role of benzodiazepines in treating anxiety disorders, β-carbolines, spanning a spectrum from full agonists to full inverse agonists at the benzodiazepine allosteric site for the GABA_A receptor, can provide valuable insight into the neural mechanisms underlying anxiety-related physiology and behavior. FG-7142 is a partial inverse agonist at the benzodiazepine allosteric site with its highest affinity for the α1 subunit-containing GABA_A receptor, although it is not selective. FG-7142 also has its highest efficacy for modulation of GABA-induced chloride flux mediated at the α1 subunit-containing GABA_A receptor. FG-7142 activates a recognized anxiety-related neural network and interacts with serotonergic, dopaminergic, cholinergic, and noradrenergic modulatory systems within that network. FG-7142 has been shown to induce anxiety-related behavioral and physiological responses in a variety of experimental paradigms across numerous mammalian and non-mammalian species, including humans. FG-7142 has proconflict actions across anxiety-related behavioral paradigms, modulates attentional processes, and increases cardioacceleratory sympathetic reactivity and neuroendocrine reactivity. Both acute and chronic FG-7142 treatment are proconvulsive, upregulate cortical adrenoreceptors, decrease subsequent actions of GABA and β-carboline agonists, and increase the effectiveness of subsequent GABA_A receptor antagonists and β-carboline inverse agonists. FG-7142, as a partial inverse agonist, can help to elucidate individual components of full agonism of benzodiazepine binding sites and may serve to identify the specific GABA_A receptor subtypes involved in specific behavioral and physiological responses.</p>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"13 4","pages":"475-501"},"PeriodicalIF":0.0,"publicationDate":"2007-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.00025.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27117133","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}

{"title":"SUBJECT INDEX FOR VOLUME 13","authors":"","doi":"10.1111/j.1527-3458.2007.suindex_1.x","DOIUrl":"https://doi.org/10.1111/j.1527-3458.2007.suindex_1.x","url":null,"abstract":"","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"13 4","pages":"504-506"},"PeriodicalIF":0.0,"publicationDate":"2007-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.suindex_1.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"137638837","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}

{"title":"Ginsenosides: Are Any of them Candidates for Drugs Acting on the Central Nervous System?","authors":"Seung-Yeol Nah,&nbsp;Dong-Hyun Kim,&nbsp;Hyewhon Rhim","doi":"10.1111/j.1527-3458.2007.00023.x","DOIUrl":"10.1111/j.1527-3458.2007.00023.x","url":null,"abstract":"<p>The last two decades have shown a marked expansion in the number of publications regarding the effects of <i>Panax ginseng</i>. Ginsenosides, which are unique saponins isolated from <i>Panax ginseng</i>, are the pharmacologically active ingredients in ginseng, responsible for its effects on the central nervous system (CNS) and the peripheral nervous system. Recent studies have shown that ginsenosides regulate various types of ion channels, such as voltage-dependent and ligand-gated ion channels, in neuronal and heterologously expressed cells. Ginsenosides inhibit voltage-dependent Ca²⁺, K⁺, and Na⁺ channel activities in a stereospecific manner. Ginsenosides also inhibit ligand-gated ion channels such as N-methyl-<span>d</span>-aspartate, some subtypes of nicotinic acetylcholine, and 5-hydroxytryptamine type 3 receptors. Competition and site-directed mutagenesis experiments revealed that ginsenosides interact with ligand-binding sites or channel pore sites and inhibit open states of ion channels. This review will introduce recent findings and advances on ginsenoside-induced regulation of ion channel activities in the CNS, and will further expand the possibilities that ginsenosides may be useful and potentially therapeutic choices in the treatment of neurodegenerative disorders.</p>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"13 4","pages":"381-404"},"PeriodicalIF":0.0,"publicationDate":"2007-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.00023.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27116732","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}

{"title":"TDIQ (5,6,7,8–tetrahydro-1,3-dioxolo [4,5-g]isoquinoline): Discovery, Pharmacological Effects, and Therapeutic Potential","authors":"Richard Young","doi":"10.1111/j.1527-3458.2007.00022.x","DOIUrl":"10.1111/j.1527-3458.2007.00022.x","url":null,"abstract":"<p>Chemically, TDIQ (5,6,7,8–tetrahydro-1,3-dioxolo[4,5-<i>g</i>]isoquinoline) can be viewed as a conformationally restricted phenylalkylamine that is related in structure to amphetamine but does not stimulate (or depress) locomotor activity in rodents. In radioligand binding studies TDIQ displays selective affinity for α₂-adrenergic receptor subsites (i.e., α_2A-, α_2B-, and α_2C-adrenergic receptors), and behavioral data suggest that it might exert an agonist (or partial agonist) effect at α₂-adrenergic receptors or interact at α₂-adrenergic heteroreceptors. Drug discrimination studies in rats indicate that TDIQ: (1) serves as a discriminative stimulus, (2) may be useful in the treatment of symptoms associated with the abuse of cocaine, and (3) exhibits a low potential for abuse. In addition, TDIQ exhibits a dose-dependent and wide dissociation between doses that produce an anxiolytic-like effect or an inhibition of “snack” consumption in mice and doses that produce minimal, if any, effects in tests that measure a potential for disruption of coordinated movement or motor activity. Also, TDIQ displays negligible effects on the heart rate (HR) and blood pressure (BP) of mice. Taken together, the preclinical data suggest that TDIQ exhibits a favorable ratio of therapeutic-like effects (anxiolytic, therapeutic adjunct in the treatment of cocaine abuse, and appetite suppression) to side effect-like activities (behavioral impairment, drug abuse, or adverse cardiovascular effect). As such, TDIQ could: (1) be a forerunner for a new type of chemical entity in the treatment of certain forms of anxiety and/or obesity and (2) serve as a structural template in the discovery and development of additional agents that might be selective for α₂-adrenergic receptors.</p>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"13 4","pages":"405-422"},"PeriodicalIF":0.0,"publicationDate":"2007-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.00022.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27116733","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}

{"title":"The Preclinical Properties of a Novel Group II Metabotropic Glutamate Receptor Agonist LY379268","authors":"Gabor Imre","doi":"10.1111/j.1527-3458.2007.00024.x","DOIUrl":"10.1111/j.1527-3458.2007.00024.x","url":null,"abstract":"<p>Activation of group II metabotropic glutamate (mGlu2/3) receptors reduces excessive glutamate release that is often associated with neurodegenerative and psychiatric disorders. This finding encouraged the search for potent and selective agonists as potential therapeutic agents. The search led to the discovery of LY379268 {(-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylic acid}, which is a highly potent and systemically available mGlu2/3 receptor agonist. LY379268 was effective in several animal models of stroke, epilepsy, drug abuse, schizophrenia, and pain. Suppression of motor activity is the major side effect of LY379268. Upon repeated administration tolerance develops to this side effect, while the therapeutic effects of LY379268 remain. To date, no clinical data with LY379268 are available. This review article summarizes the preclinical pharmacology of LY379268.</p>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"13 4","pages":"444-464"},"PeriodicalIF":0.0,"publicationDate":"2007-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.00024.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27116735","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}

{"title":"Catechol-O-methyltransferase and Its Inhibitors in Parkinson's Disease","authors":"Maria João Bonifácio,&nbsp;P. Nuno Palma,&nbsp;Luís Almeida,&nbsp;Patrício Soares-da-Silva","doi":"10.1111/j.1527-3458.2007.00020.x","DOIUrl":"10.1111/j.1527-3458.2007.00020.x","url":null,"abstract":"<p>Parkinson's disease (PD) is a neurological disorder characterized by the degeneration of dopaminergic neurons, with consequent reduction in striatal dopamine levels leading to characteristic motor symptoms. The most effective treatment for this disease continues to be the dopamine replacement therapy with levodopa together with an inhibitor of aromatic amino acid decarboxylase (AADC). The efficacy of this therapy, however, decreases with time and most patients develop fluctuating responses and dyskinesias. The last decade showed that the use of catechol-<i>O</i>-methyltransferase inhibitors as adjuvants to the levodopa/AADC inhibitor therapy, significantly improves the clinical benefits of this therapy.</p><p>The purpose of this article is to review the current knowledge on the enzyme catechol-<i>O</i>-methyltransferase (COMT) and the role of COMT inhibitors in PD as a new therapeutic approach to PD involving conversion of levodopa to dopamine at the target region in the brain and facilitation of the continuous action of this amine at the receptor sites. A historical overview of the discovery and development of COMT inhibitors is presented with a special emphasis on nebicapone, presently under clinical development, as well as entacapone and tolcapone, which are already approved as adjuncts in the therapy of PD. This article reviews human pharmacokinetic and pharmacodynamic properties of these drugs as well as their clinical efficacy and safety.</p>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"13 3","pages":"352-379"},"PeriodicalIF":0.0,"publicationDate":"2007-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.00020.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40993420","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}