CNS drug reviews最新文献

{"title":"CGP7930: A Positive Allosteric Modulator of the GABAB Receptor","authors":"C. L. Adams,&nbsp;A. J. Lawrence","doi":"10.1111/j.1527-3458.2007.00021.x","DOIUrl":"10.1111/j.1527-3458.2007.00021.x","url":null,"abstract":"<p>CGP7930 (3-(3′,5′-Di-<i>tert</i>-butyl-4′-hydroxy)phenyl-2,2-dimethylpropanol) is a positive allosteric modulator of the metabotropic GABA_B receptor. CGP7930 has been found to modulate the GABA_B receptor in the open, or high affinity, state increasing agonist affinity for the receptor and signal transduction efficacy following agonist stimulation. The GABA_B heteromeric subunit B2, involved in signal transduction but not ligand binding, seems to be the site of action of CGP7930 and similar allosteric modulators. When administered alone in naïve animals, CGP7930 acts as an anxiolytic in rodents without other overt behavioral effects and has also been demonstrated to reduce self-administration of nicotine, cocaine, or alcohol in rodents, suggesting that “fine tuning” of the GABA_B receptor by positive allosteric modulators may be able to regulate abuse of these drugs. Baclofen, the GABA_B agonist, is currently finding use in treating addiction and various other disorders, but this can result in off-target effects and tolerance. CGP7930 when co-administered with baclofen enhances its potency, which could in theory minimize deleterious effects. Further study of CGP7930 is required, but this compound, and others like it, holds potential in a clinical setting.</p>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.00021.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40994006","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":"Lig-8, a Highly Bioactive Lignophenol Derivative from Bamboo Lignin, Exhibits Multifaceted Neuroprotective Activity","authors":"Yasushi Ito,&nbsp;Yukihiro Akao,&nbsp;Masamitsu Shimazawa,&nbsp;Norio Seki,&nbsp;Yoshinori Nozawa,&nbsp;Hideaki Hara","doi":"10.1111/j.1527-3458.2007.00017.x","DOIUrl":"10.1111/j.1527-3458.2007.00017.x","url":null,"abstract":"<p>Lignin is a durable aromatic network polymer that is second only to cellulose in natural abundance. Lig-8, a lignophenol derivative from bamboo lignin, is a highly potent neuroprotectant. It protects human neuroblastoma cells (SH-SY5Y) from hydrogen peroxide (H₂O₂)–induced apoptosis by preventing caspase-3 activation via either caspase-8 or caspase-9. It exerts this antiapoptotic effect by protecting mitochondrial membrane permeability from damage by H₂O₂ or the peripheral benzodiazepine receptor ligand PK11195. Lig-8 has been also shown to scavenge the reactive oxygen or nitrogen species <i>in vitro</i>. Furthermore, lig-8 suppresses apoptosis induced by oxygen-glucose deprivation, tunicamycin (endoplasmic reticulum [ER]–stress inducer), or proteasome inhibitor in pheochromocytoma cells. In addition, <i>in vivo</i>, lig-8 reduced intravitreal <i>N</i>-methyl-<span>d-</span>aspartate–induced retinal damage (decreases in retinal ganglion cells and inner plexiform layer thickness) in mice. Lig-8 prevents neuronal damage partly by inhibiting excessive endoplasmic reticulum stress. In this article, we review the protective effects of lig-8 against apoptosis induced by various stimuli. Apoptosis is an active, energy-dependent process through which living cells initiate their own death. It can be induced by a variety of physiological and pharmacological stimuli. Apoptotic cell death is associated with neurodegenerative disorders such as Alzheimer, Parkinson, or Huntington disease as well as glaucoma. We believe that the elucidation of the mechanism of antiapoptotic action of lig-8 may help in finding new approaches to the treatment of neurodegenerative disorders.</p>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.00017.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40994005","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":"Pharmacological Properties of BN82451: A Novel Multitargeting Neuroprotective Agent","authors":"Pierre Etienne Chabrier,&nbsp;Michel Auguet","doi":"10.1111/j.1527-3458.2007.00018.x","DOIUrl":"10.1111/j.1527-3458.2007.00018.x","url":null,"abstract":"<p>BN82451 belongs to a new family of small molecules designated as multitargeting or hybrid molecules. BN82451 is orally active, has good central nervous system penetration, and elicits potent neuronal protection and antiinflammatory properties. Neuronal protection is due to Na⁺ channel blockade, antioxidant properties, and mitochondria-protecting activity, whereas inhibition of cyclooxygenases is mostly responsible for its antiinflammatory activity. BN82451 has been shown to exert a potent neuroprotective effect in various <i>in vitro</i> and <i>in vivo</i> animal models. BN82451 was found to exert a significant protection in experimental animal models mimicking aspects of cerebral ischemia, Parkinson disease, Huntington disease, and more particularly amyotrophic lateral sclerosis. Collectively, its pharmacological properties designate BN82451 as a promising neuroprotective agent.</p>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.00018.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40994007","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":"Nitroparacetamol (NCX-701) and Pain: First in a Series of Novel Analgesics","authors":"E. Alfonso Romero-Sandoval,&nbsp;M. Mar Curros-Criado,&nbsp;Gema Gaitan,&nbsp;Carlos Molina,&nbsp;Juan F. Herrero","doi":"10.1111/j.1527-3458.2007.00016.x","DOIUrl":"10.1111/j.1527-3458.2007.00016.x","url":null,"abstract":"<p>The combination of numerous classic drugs with nitric oxide donors has led to the development of new compounds with promising therapeutic activities in a great variety of situations, including cardiovascular and respiratory systems, ocular pressure, inflammation, and pain. One of the first compounds developed was NCX-701 or nitroparacetamol, resulting from the combination of paracetamol, a classic and popular analgesic used in a great number of over-the-counter medications because of its antipyretic and analgesic properties, and a nitrooxybutyroyl moiety, which releases nitric oxide at a low but steady level. Although paracetamol is devoid of most of the gastrointestinal toxicity associated with aspirin-like drugs, this type of compounds was first designed to take advantage of the cytoprotective properties of nitric oxide when released at low concentrations. However, the combination of these molecules also resulted in an unexpected enhancement of the analgesic activity of paracetamol. In fact, NCX-701 has been shown to be effective in acute nociception as well as in neuropathic pain, situations in which paracetamol and other COX inhibitors are devoid of any effect. In addition, NCX-701 is more potent and, in some circumstances, more effective than its parent compound in different models of inflammatory pain. Furthermore, whereas paracetamol lacks any effective antiinflammatory action, NCX-701 might reduce inflammation. All these results taken together imply that the mechanism of action of NCX-701 is different from that of paracetamol, although it is not yet established for either molecule. NCX-701 appears to be a promising compound in the treatment of different types of pain, with a likely better profile of side effects than its parent molecule, paracetamol. Although recent clinical trials provided data consistent with the preclinical profile of NCX-701, further studies are needed to support its clinical use.</p>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.00016.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40994004","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":"Neuroprotective Effects of Propofol in Acute Cerebral Injury","authors":"Chiara Adembri,&nbsp;Luna Venturi,&nbsp;Domenico E. Pellegrini-Giampietro","doi":"10.1111/j.1527-3458.2007.00015.x","DOIUrl":"10.1111/j.1527-3458.2007.00015.x","url":null,"abstract":"<p>Propofol (2,6-diisopropylphenol) is one of the most popular agents used for induction of anesthesia and long-term sedation, owing to its favorable pharmacokinetic profile, which ensures a rapid recovery even after prolonged administration. A neuroprotective effect, beyond that related to the decrease in cerebral metabolic rate for oxygen, has been shown to be present in many <i>in vitro</i> and <i>in vivo</i> established experimental models of mild/moderate acute cerebral ischemia. Experimental studies on traumatic brain injury are limited and less encouraging. Despite the experimental results and the positive effects on cerebral physiology (propofol reduces cerebral blood flow but maintains coupling with cerebral metabolic rate for oxygen and decreases intracranial pressure, allowing optimal intraoperative conditions during neurosurgical operations), no clinical study has yet indicated that propofol may be superior to other anesthetics in improving the neurological outcome following acute cerebral injury. Therefore, propofol cannot be indicated as an established clinical neuroprotectant per se, but it might play an important role in the so-called multimodal neuroprotection, a global strategy for the treatment of acute injury of the brain that includes preservation of cerebral perfusion, temperature control, prevention of infections, and tight glycemic control.</p>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.00015.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40994008","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":"RB101-mediated Protection of Endogenous Opioids: Potential Therapeutic Utility?","authors":"Emily M. Jutkiewicz","doi":"10.1111/j.1527-3458.2007.00011.x","DOIUrl":"10.1111/j.1527-3458.2007.00011.x","url":null,"abstract":"<p>The endogenous opioids met- and leu-enkephalin are inactivated by peptidases preventing the activation of opioid receptors. Inhibition of enkephalin-degrading enzymes increases endogenous enkephalin levels and stimulates robust behavioral effects. RB101, an inhibitor of enkephalin-degrading enzymes, produces antinociceptive, antidepressant, and anxiolytic effects in rodents, without typical opioid-related negative side effects. Although enkephalins are not selective endogenous ligands, RB101 induces these behaviors through receptor-selective activity. The antinociceptive effects of RB101 are produced through either the mu-opioid receptor alone or through activation of both mu- and delta-opioid receptors; the antidepressant-like and anxiolytic effects of RB101 are mediated only through the delta-opioid receptor. Although little is known about the effects of RB101 on other physiologically and behaviorally relevant peptides, these findings suggest that RB101 and other inhibitors of enkephalin-degrading enzymes may have potential as novel therapeutic compounds for the treatment of pain, depression, and anxiety.</p>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.00011.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26826150","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":"Characterization of the Potent 5-HT1A /B Receptor Antagonist and Serotonin Reuptake Inhibitor SB-649915: Preclinical Evidence for Hastened Onset of Antidepressant/Anxiolytic Efficacy","authors":"Jeannette M. Watson,&nbsp;Lee A. Dawson","doi":"10.1111/j.1527-3458.2007.00012.x","DOIUrl":"10.1111/j.1527-3458.2007.00012.x","url":null,"abstract":"<p>An increase in brain serotonin (5-HT) levels is thought to be a key mechanism of action responsible for generating antidepressant efficacy. It has been proven that selective serotonin reuptake inhibitors are effective antidepressants, but the delay to therapeutic onset of these agents is thought to be due to the time required for 5-HT_1A, and possibly 5-HT_1B, autoreceptors to desensitize. Therefore, an agent incorporating 5-HT reuptake inhibition coupled with 5-HT_1A and/or 5-HT_1B autoreceptor antagonism may provide a fast-acting clinical agent. The current studies review the profile of SB-649915 (6-[(1-{2-[(2-methylquinolin-5-yl)oxy]ethyl}piperidin-4-yl)methyl]-2<i>H</i>-1,4-benzoxazin-3(4<i>H</i>)-one), a novel compound with high affinity for human (h) 5-HT_1A and 5-HT_1B receptors (pK_i values of 8.6 and 8.0, respectively) as well as the (h) 5-HT transporter (SERT) (pK_i value of 9.3). SB-649915 behaved as an antagonist at both 5-HT_1A and 5-HT_1B receptors <i>in vitro</i> and <i>in vivo,</i> reversing 5-HT, (+)8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and SKF99101-induced functional/behavioral responses. Furthermore, it inhibited [³H]5-HT reuptake in rat cortical synaptosomes, <i>in vitro</i> and <i>ex vivo</i>. In electrophysiological studies SB-649915 had no effect on rat dorsal raphe neuronal cell firing <i>per se,</i> but reversed 8-OH-DPAT–induced inhibition of firing both <i>in vitro</i> and <i>in vivo</i>. In addition, in a microdialysis study, it produced an acute increase in extracellular 5-HT in forebrain structures of the rat. Finally, SB-649915 demonstrated acute anxiolytic activity in both rodent and non-human primate and reduced the latency to onset of anxiolytic behavior, compared to paroxetine, in the rat social interaction paradigm. In summary, SB-649915 is a novel, potent 5-HT_1A/1B autoreceptor antagonist, and 5-HT reuptake inhibitor. This particular pharmacological profile provides a novel mechanism that could offer fast-acting antidepressant activity.</p>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.00012.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26826151","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":"DP-155, a Lecithin Derivative of Indomethacin, is a Novel Nonsteroidal Antiinflammatory Drug for Analgesia and Alzheimer's Disease Therapy","authors":"Eran Dvir,&nbsp;Anat Elman,&nbsp;Danielle Simmons,&nbsp;Israel Shapiro,&nbsp;Revital Duvdevani,&nbsp;Arik Dahan,&nbsp;Amnon Hoffman,&nbsp;Jonathan E. Friedman","doi":"10.1111/j.1527-3458.2007.00014.x","DOIUrl":"10.1111/j.1527-3458.2007.00014.x","url":null,"abstract":"<p>DP-155 is a lipid prodrug of indomethacin that comprises the latter conjugated to lecithin at position <i>sn</i>-2 via a 5-carbon length linker. It is cleaved by phospholipase A₂ (PLA)₂ to a greater extent than similar compounds with linkers of 2, 3, and 4 carbons. Indomethacin is the principal metabolite of DP-155 in rat serum and, after DP-155 oral administration, the half-life of the metabolite was 22 and 93 h in serum and brain, respectively, compared to 10 and 24 h following indomethacin administration. The brain to serum ratio was 3.5 times higher for DP-155 than for indomethacin. <i>In vitro</i> studies demonstrated that DP-155 is a selective cyclooxygenase (COX)-2 inhibitor. After it is cleaved, its indomethacin derivative nonselectively inhibits both COX-1 and -2. DP-155 showed a better toxicity profile probably due to the sustained, low serum levels and reduced maximal concentration of its indomethacin metabolite. DP-155 did not produce gastric toxicity at the highest acute dose tested (0.28 mmol/kg), while indomethacin caused gastric ulcers at a dose 33-fold lower. Furthermore, after repeated oral dosing, gastrointestinal and renal toxicity was lower (10- and 5-fold, respectively) and delayed with DP-155 compared to indomethacin. In addition to reduced toxicity, DP-155 had similar ameliorative effects to indomethacin in antipyretic and analgesia models. Moreover, DP-155 and indomethacin were equally efficacious in reducing levels of amyloid ß (Aß)42 in transgenic Alzheimer's disease mouse (Tg2576) brains as well as reducing Aß42 intracellular uptake, neurodegeneration, and inflammation in an <i>in vitro</i> AD model. The relatively high brain levels of indomethacin after DP-155 administration explain the equal efficacy of DP-155 despite its low systemic blood concentrations. Compared to indomethacin, the favored safety profile and equal efficacy of DP-155 establish the compound as a potential candidate for chronic use to treat AD-related pathology and for analgesia.</p>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.00014.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26826154","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":"Pharmacological Actions of NGB 2904, a Selective Dopamine D3 Receptor Antagonist, in Animal Models of Drug Addiction","authors":"Zheng-Xiong Xi,&nbsp;Eliot L. Gardner","doi":"10.1111/j.1527-3458.2007.00013.x","DOIUrl":"10.1111/j.1527-3458.2007.00013.x","url":null,"abstract":"<p>As a continuation of our work with SB-277011A, we have examined the effects of another highly elective dopamine (DA) D₃ receptor antagonist, N-(4-[4-{2,3-dichlorophenyl}-1-piperazinyl]butyl)-2-fluorenylcarboxamide (NGB 2904), in animal models of addiction. Our results indicate that by systemic administration, NGB 2904 inhibits intravenous cocaine self-administration maintained under a progressive-ratio (PR) reinforcement schedule, cocaine- or cocaine cue–induced reinstatement of cocaine-seeking behavior, and cocaine- or other addictive drug-enhanced brain stimulation reward (BSR). The action of NGB 2904 on PR cocaine self-administration was long-lasting (1–2 days) after a single injection, supporting its potential use in treatment of cocaine addiction. The effects of NGB 2904 in the BSR paradigm were dose-dependent for both NGB 2904 and cocaine; that is, only lower doses of NGB 2904 were effective, and their putative antiaddiction effect could be overcome by increasing the doses of cocaine or other addictive drugs. A dopamine-dependent mechanism is proposed to explain the effects of NGB 2904 on cocaine's actions in these animal models of drug addiction. The data reviewed in this paper suggest that NGB 2904 or other D₃-selective antagonists may have potential in controlling motivation for drug-taking behavior or relapse to drug-seeking behavior, but may have a limited role in antagonizing the acute rewarding effects produced by cocaine or other addictive drugs. In addition, NGB 2904 may also act as a useful tool to study the role of D₃ receptors in drug addiction.</p>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.00013.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26826153","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":"Glatiramer Acetate in Multiple Sclerosis: A Review","authors":"Maddalena Ruggieri,&nbsp;Carlo Avolio,&nbsp;Paolo Livrea,&nbsp;Maria Trojano","doi":"10.1111/j.1527-3458.2007.00010.x","DOIUrl":"10.1111/j.1527-3458.2007.00010.x","url":null,"abstract":"<p>Multiple sclerosis (MS) is considered to be primarily an inflammatory autoimmune disease. Over the last 5 years, our view of the pathogenesis of MS has evolved considerably. The axonal damage was recognized as an early event in the disease process and as an important determinant of long-term disability. Therefore, the antiinflammatory and neuroprotective strategies are thought to represent promising approach to the therapy of MS. The therapeutic potential of glatiramer acetate (GA), a synthetic amino acid polymer composed of a mixture of <span>l</span>-glutamic acid, <span>l</span>-lysine, <span>l</span>-alanine, and <span>l</span>-tyrosine in defined proportions, in MS has been apparent for many years. GA has been shown to be effective in preventing and suppressing experimental allergic encephalomyelitis (EAE), the animal model of MS. GA has been, therefore, evaluated in several clinical studies and found to alter the natural history of relapsing-remitting (RR)MS by reducing the relapse rate and affecting disability. These findings were confirmed in open-label follow-up trials covering more than 10 years of treatment. The trials demonstrated sustained efficacy for GA in slowing the progression of disability. The clinical therapeutic effect of GA is consistent with the results of magnetic resonance imaging (MRI) findings from various clinical centers. At a daily standard dose of 20 mg, s.c., GA was generally well tolerated. The induction of GA-reactive T-helper 2-like regulatory suppressor cells is thought to be the main mechanism of the therapeutic action of this drug. In addition, it was recently shown that GA-reactive T cells produce neurotrophic factors (e.g., brain-derived neurotrophic factor [BDNF]) that protect neurons and axons in the area of injury.</p>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2007-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2007.00010.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26827870","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}