Genomes and Genes
central nervous system agents
Summary: A class of drugs producing both physiological and psychological effects through a variety of mechanisms. They can be divided into "specific" agents, e.g., affecting an identifiable molecular mechanism unique to target cells bearing receptors for that agent, and "nonspecific" agents, those producing effects on different target cells and acting by diverse molecular mechanisms. Those with nonspecific mechanisms are generally further classed according to whether they produce behavioral depression or stimulation. Those with specific mechanisms are classed by locus of action or specific therapeutic use. (From Gilman AG, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p252)
- Pardridge W. The blood-brain barrier and neurotherapeutics. NeuroRx. 2005;2:1-2 pubmed
- Hurko O, Ryan J. Translational research in central nervous system drug discovery. NeuroRx. 2005;2:671-82 pubmed..Implementation of new technologies is the key to success in this emerging endeavor. ..
- Pangalos M, Schechter L, Hurko O. Drug development for CNS disorders: strategies for balancing risk and reducing attrition. Nat Rev Drug Discov. 2007;6:521-32 pubmed
- Chang Y, Huang W, Tien L, Wang S. Ginsenosides Rg1 and Rb1 enhance glutamate release through activation of protein kinase A in rat cerebrocortical nerve terminals (synaptosomes). Eur J Pharmacol. 2008;578:28-36 pubmed..This finding might provide important information regarding the action of ginseng in the central nervous system. ..
- Kreuter J. Influence of the surface properties on nanoparticle-mediated transport of drugs to the brain. J Nanosci Nanotechnol. 2004;4:484-8 pubmed..quot; The drug, then, may be released either within these cells followed by passive diffusion into the brain or be transported into the brain by transcytosis. ..
- Patel M, Goyal B, Bhadada S, Bhatt J, Amin A. Getting into the brain: approaches to enhance brain drug delivery. CNS Drugs. 2009;23:35-58 pubmed publisher..The current challenge is to develop drug delivery strategies that will allow the passage of drug molecules through the BBB in a safe and effective manner. ..
- Prokai Tatrai K, Prokai L. Prodrugs of thyrotropin-releasing hormone and related peptides as central nervous system agents. Molecules. 2009;14:633-54 pubmed publisher..The value of prodrug-amenable analogues as potential drug-like central nervous systems agents was highlighted. ..
- Begley D. Delivery of therapeutic agents to the central nervous system: the problems and the possibilities. Pharmacol Ther. 2004;104:29-45 pubmed..The various strategies available and under development for enhancing drug delivery to the CNS are reviewed. ..
- Radad K, Gille G, Moldzio R, Saito H, Rausch W. Ginsenosides Rb1 and Rg1 effects on mesencephalic dopaminergic cells stressed with glutamate. Brain Res. 2004;1021:41-53 pubmed..Thus our study indicates that ginsenosides Rb1 and Rg1 have a partial neurotrophic and neuroprotective role in dopaminergic cell culture. ..
- Blasi P, Giovagnoli S, Schoubben A, Ricci M, Rossi C. Solid lipid nanoparticles for targeted brain drug delivery. Adv Drug Deliv Rev. 2007;59:454-77 pubmed..A critical consideration on the potential application of such technology as related to the current status of brain drug development is also given. ..
- Leung K, Pon Y, Wong R, Wong A. Ginsenoside-Rg1 induces vascular endothelial growth factor expression through the glucocorticoid receptor-related phosphatidylinositol 3-kinase/Akt and beta-catenin/T-cell factor-dependent pathway in human endothelial cells. J Biol Chem. 2006;281:36280-8 pubmed..In addition, the GR antagonist RU486 was able to inhibit Rg1-induced PI3K/Akt and beta-catenin activation. These findings provide new insights into the mechanism responsible for Rg1 functions. ..
- Alavijeh M, Chishty M, Qaiser M, Palmer A. Drug metabolism and pharmacokinetics, the blood-brain barrier, and central nervous system drug discovery. NeuroRx. 2005;2:554-71 pubmed..This review focuses on BBB penetration, along with pharmacokinetics and drug metabolism, in the process of the discovery and development of safe and effective medicines for CNS disorders. ..
- Tsuji A. Small molecular drug transfer across the blood-brain barrier via carrier-mediated transport systems. NeuroRx. 2005;2:54-62 pubmed
- Anderson P, Manoguerra A, ValdÃ©s V. A Review of Adverse Reactions in Infants From Medications in Breastmilk. Clin Pediatr (Phila). 2016;55:236-44 pubmed publisher..A few narrowly focused studies are now available on long-term effects of maternal drug therapy on breastfed infants and they are mostly reassuring. ..
- Paintlia A, Paintlia M, Mohan S, Singh A, Singh I. AMP-activated protein kinase signaling protects oligodendrocytes that restore central nervous system functions in an experimental autoimmune encephalomyelitis model. Am J Pathol. 2013;183:526-41 pubmed publisher..We conclude that AMPK activators, including metformin, have the potential to limit neurologic deficits in multiple sclerosis and related neurodegenerative disorders. ..
- Burne T, Johnston A, Wilkinson L, Kendrick K. Effects of anesthetic agents on socially transmitted olfactory memories in mice. Neurobiol Learn Mem. 2010;93:268-74 pubmed publisher..Thus, we have shown that under certain conditions it is possible for an anesthetized observer mouse to learn a preference or aversion of a socially-linked olfactory cue. ..
- Tachikawa M, Uchida Y, Terasaki T. [Multi-disciplinary research approaches on the brain barrier transport system, a dynamic interface]. Brain Nerve. 2013;65:121-36 pubmed
- Soeter M, Kindt M. Dissociating response systems: erasing fear from memory. Neurobiol Learn Mem. 2010;94:30-41 pubmed publisher..From a clinical and ethical perspective, disrupting reconsolidation points to promising interventions persistently erasing fear responses from trauma memory without affecting the actual recollection. ..
- Leone S, Noera G, Bertolini A. Melanocortins as innovative drugs for ischemic diseases and neurodegenerative disorders: established data and perspectives. Curr Med Chem. 2013;20:735-50 pubmed
- Wong Y, Qian S, Zuo Z. Regioselective biotransformation of CNS drugs and its clinical impact on adverse drug reactions. Expert Opin Drug Metab Toxicol. 2012;8:833-54 pubmed publisher..Administrating drugs by alternative routes such as the intranasal, transdermal, sublingual, and buccal routes could also be a strategy to reduce unwanted metabolite formations. ..
- Bijlsma E, Olivier B, Groenink L. Cocaine-induced changes in affective state modulate the light-enhanced startle response. Behav Brain Res. 2010;213:117-20 pubmed publisher..The finding that both cocaine-induced positive and negative affect can be detected in LES, suggests that this may be a valuable tool in studying affect regulation in rodents. ..
- Liu Z, Zhao M, Zhang Y, Xue J, Chen N. Ginsenoside Rg1 promotes glutamate release via a calcium/calmodulin-dependent protein kinase II-dependent signaling pathway. Brain Res. 2010;1333:1-8 pubmed publisher..Combined with our previous study on Rb1, these two studies altogether indicated that different ginsenosides may promote neurotransmitter release via differential signaling pathways. ..
- Lanius R, Brewin C, Bremner J, Daniels J, Friedman M, Liberzon I, et al. Does neuroimaging research examining the pathophysiology of posttraumatic stress disorder require medication-free patients?. J Psychiatry Neurosci. 2010;35:80-9 pubmed..Neuroimaging studies should also take into account whether patients are currently engaged in psychotherapeutic treatment. ..
- Bishop G, Scheiber I, Dringen R, Robinson S. Synergistic accumulation of iron and zinc by cultured astrocytes. J Neural Transm (Vienna). 2010;117:809-17 pubmed publisher..These mechanisms may be involved in disorders that involve elevations in the extracellular concentrations of these metal ions...
- Marchant N, Whitaker L, Bossert J, Harvey B, Hope B, Kaganovsky K, et al. Behavioral and Physiological Effects of a Novel Kappa-Opioid Receptor-Based DREADD in Rats. Neuropsychopharmacology. 2016;41:402-9 pubmed publisher..Our results indicate that the novel KORD is a promising tool to selectively inactivate brain areas and neural circuits in rat studies of motivated behavior. ..
- Geerts H. Of mice and men: bridging the translational disconnect in CNS drug discovery. CNS Drugs. 2009;23:915-26 pubmed publisher..This includes the development of hybrid computational models, based upon documented preclinical physiology and pharmacology, but populated and validated with clinical data from actual patients. ..
- Tommelein E, Mehuys E, Petrovic M, Somers A, Van Damme C, Pattyn E, et al. Potentially inappropriate prescribing in nursing home residents detected with the community pharmacist specific GheOP(3)S-tool. Int J Clin Pharm. 2016;38:1063-8 pubmed publisher..This finding urges for initiatives on the patient-level, but also on a broader, institutional level. ..
- Healy A, Rush R, Ocain T. Fragile X syndrome: an update on developing treatment modalities. ACS Chem Neurosci. 2011;2:402-10 pubmed publisher..Moreover, pharmaceutical therapies targeting the most common form of inherited ID, Fragile X syndrome (FXS), may become the new benchmark for central nervous system (CNS) drug discovery: seeking cures for neurodevelopmental disorders...
- Lanevskij K, Japertas P, Didziapetris R. Improving the prediction of drug disposition in the brain. Expert Opin Drug Metab Toxicol. 2013;9:473-86 pubmed publisher..To increase the efficiency of computational tools, a broader view is necessary, involving rate and extent of brain penetration, as well as plasma and brain tissue binding strength, instead of relying on any single property. ..
- Simonovitch S, Schmukler E, Bespalko A, Iram T, Frenkel D, Holtzman D, et al. Impaired Autophagy in APOE4 Astrocytes. J Alzheimers Dis. 2016;51:915-27 pubmed publisher..This suggests that impaired autophagy may play a role in mediating the pathological effects of ApoE4 in AD. ..
- Chico L, WATTERSON D. The 6th drug discovery for neurodegeneration conference: an intensive course on translating research into drugs. Expert Opin Drug Discov. 2012;7:1225-8 pubmed publisher..This workshop has evolved to serve a critical educational need, with a wide range of investigator participation. ..
- Lingford Hughes A, Watson B, Kalk N, Reid A. Neuropharmacology of addiction and how it informs treatment. Br Med Bull. 2010;96:93-110 pubmed publisher..In addition to modulating this reward pathway, alternative approaches in the future will target learning and memory, improving impulse control and decision-making. ..
- Gielen M. [Molecular operation of ionotropic glutamate receptors: proteins that mediate the excitatory synaptic neurotransmission]. Med Sci (Paris). 2010;26:65-72 pubmed publisher..This could prove useful for the discovery of drugs of therapeutic interest, such as cognitive enhancers, pain killers or anti-psychotics. ..
- Ott R, Lenk C, Miller N, Neuhaus Bühler R, Biller Andorno N. Neuroenhancement - perspectives of Swiss psychiatrists and general practitioners. Swiss Med Wkly. 2012;142:w13707 pubmed publisher..A minority would follow a consumer model that leaves the decision about the use of neuroenhancers to the client, even though this conflicts with legal requirements regarding drug prescriptions. ..
- Alelyunas Y, Empfield J, McCarthy D, Spreen R, Bui K, Pelosi Kilby L, et al. Experimental solubility profiling of marketed CNS drugs, exploring solubility limit of CNS discovery candidate. Bioorg Med Chem Lett. 2010;20:7312-6 pubmed publisher..Only seven drugs had solubility <10 ?M. Using these data, we established a solubility criterion to support CNS discovery. The implication of poor solubility with potential safety concerns and undesirable side effects are discussed. ..
- Saniotis A, Irvine R. Climate change and the possible health effects on older Australians. Aust J Prim Health. 2010;16:217-20 pubmed publisher..This paper discusses two issues in relation to climate change and older Australians: first, pharmacology and autoregulation; and second, mental health among older Australians. ..
- Backholer K, Bowden M, Gamber K, Bjørbaek C, Iqbal J, Clarke I. Melanocortins mimic the effects of leptin to restore reproductive function in lean hypogonadotropic ewes. Neuroendocrinology. 2010;91:27-40 pubmed publisher..Melanocortin treatment restores LH secretion in lean animals. ..
- Marks K, Kearns D, Christensen C, Silberberg A, Weiss S. Learning that a cocaine reward is smaller than expected: A test of Redish's computational model of addiction. Behav Brain Res. 2010;212:204-7 pubmed publisher..Instead, the present results suggest that standard error-correction learning rules apply even to drug reinforcers. ..
- Urban M, Navratil T, Pelclova D. Trends in CNS affecting drugs in the calls to the Toxicological Information Center from 1997 to 2012. Neuro Endocrinol Lett. 2013;34 Suppl 2:25-30 pubmed..4%). The current drugs prescription with improved safety profiles brings the beneficial effect of lowering the severity of poisonings and better prognosis of intoxications as observed in the TIC statistics. ..
- Wager T, Kormos B, Brady J, Will Y, Aleo M, Stedman D, et al. Improving the odds of success in drug discovery: choosing the best compounds for in vivo toxicology studies. J Med Chem. 2013;56:9771-9 pubmed publisher..This trend held across a wide range of CNS modes of action, encompassing targets such as enzymes, G-protein-coupled receptors, ion channels, and transporters. ..
- Takahashi M, Ishida M, Saito T, Ohshima T, Hisanaga S. Valproic acid downregulates Cdk5 activity via the transcription of the p35 mRNA. Biochem Biophys Res Commun. 2014;447:678-82 pubmed publisher..The chronic administration of VPA also downregulated p35 in mouse brains. These results indicate that VPA regulates Cdk5 activity in neurons via p35 transcription mediated by HDAC inhibition. ..
- Kihara A, Santos T, Osuna Melo E, Paschon V, Vidal K, Akamine P, et al. Connexin-mediated communication controls cell proliferation and is essential in retinal histogenesis. Int J Dev Neurosci. 2010;28:39-52 pubmed publisher..Taken together, our results pointed a pivotal role of Cx45 in the developing retina. Moreover, this study revealed that Cx-mediated communication is essential in retinal histogenesis, particularly in the control of cell proliferation. ..
- Augutis K, Axelsson M, Portelius E, Brinkmalm G, Andreasson U, Gustavsson M, et al. Cerebrospinal fluid biomarkers of ?-amyloid metabolism in multiple sclerosis. Mult Scler. 2013;19:543-52 pubmed publisher..We found that natalizumab therapy may be able to counteract the altered APP metabolism in MS. The CSF A? isoform distribution was found to be distinct in SPMS patients, as compared to the controls. ..
- Joshi M, Akhtar M, Najmi A, Khuroo A, Goswami D. Effect of zinc in animal models of anxiety, depression and psychosis. Hum Exp Toxicol. 2012;31:1237-43 pubmed publisher..The results obtained in this study are preliminary, as further research is required to confirm the exact role of Zn metal in the investigated central nervous system disorders. ..
- Kwon J, Kim M, Bruera S, Park M, Bruera E, Hui D. Off-Label Medication Use in the Inpatient Palliative Care Unit. J Pain Symptom Manage. 2017;54:46-54 pubmed publisher..We documented 6276 prescription events, and 2199 (35%) were off-label. Among off-label prescriptions, central nervous system agents (n = 1606, 73%), hormones and synthetic substitutes (n = 302, 14%), and autonomic drugs (n = 183,..
- Giuliano F, Droupy S. [Sexual side effects of pharmacological treatments]. Prog Urol. 2013;23:804-10 pubmed publisher..Sexual side effects of pharmacological treatments are not unusual and must be systematically surveyed in men and women complaining about sexual dysfunction. ..
- Schmidt M, Sharma A, Schifano F, Feinmann C. "Legal highs" on the net-Evaluation of UK-based Websites, products and product information. Forensic Sci Int. 2011;206:92-7 pubmed publisher..Products marketed as "legal highs" are easily available from UK-based Internet retailers and are reasonably affordable. Safety information provided to consumers is poor. Uninformed users risk serious adverse effects. ..
- Luna Tortós C, Fedrowitz M, Loscher W. Evaluation of transport of common antiepileptic drugs by human multidrug resistance-associated proteins (MRP1, 2 and 5) that are overexpressed in pharmacoresistant epilepsy. Neuropharmacology. 2010;58:1019-32 pubmed publisher..The data indicate that common AEDs are not substrates for human MRP1, MRP2 or MRP5, at least in the in vitro models used in this study. ..
- Mika J, Rojewska E, Makuch W, Przewlocka B. Minocycline reduces the injury-induced expression of prodynorphin and pronociceptin in the dorsal root ganglion in a rat model of neuropathic pain. Neuroscience. 2010;165:1420-8 pubmed publisher..Therefore, the injury-induced activation of microglia and leukocytes and the subsequent activation of neuropeptides involved in nociception processes are potential targets for the attenuation of neuropathic pain. ..
- Björk K, Svenningsson P. Modulation of monoamine receptors by adaptor proteins and lipid rafts: role in some effects of centrally acting drugs and therapeutic agents. Annu Rev Pharmacol Toxicol. 2011;51:211-42 pubmed publisher..Possible roles of adaptor proteins and lipid rafts in disease states and in mediating actions of drugs and therapeutic agents are also discussed. ..
- Ma D, Zhang M, Larsen C, Xu F, Hua W, Yamashima T, et al. DHA promotes the neuronal differentiation of rat neural stem cells transfected with GPR40 gene. Brain Res. 2010;1330:1-8 pubmed publisher..This may be involved in neuronal differentiation and neurite growth in rat neural stem cells transfected with GPR40 gene. These data provide a new sight in the future utilization of neural stem cells transplantation. ..
- Ecker C, Spooren W, Murphy D. Developing new pharmacotherapies for autism. J Intern Med. 2013;274:308-20 pubmed publisher..The EU-AIMS Initiative consists of academic and industrial partners working in collaboration to deliver a more 'personalized' approach to diagnosing and treating ASD in the future. ..
- Lund M, Petersen T, Dalhoff K. Clinical Implications of P-Glycoprotein Modulation in Drug-Drug Interactions. Drugs. 2017;77:859-883 pubmed publisher..Further, various ways of handling potential DDIs in clinical practice are described and exemplified in relation to drugs interfering with P-gp. ..
- Hersh D, Wadajkar A, Roberts N, Perez J, Connolly N, Frenkel V, et al. Evolving Drug Delivery Strategies to Overcome the Blood Brain Barrier. Curr Pharm Des. 2016;22:1177-1193 pubmed..Based on these exciting advances, we anticipate that in the near future, drug delivery research efforts will lead to more effective therapeutic interventions for diseases of the CNS. ..
- Hawley M, Morozowich W. Modifying the diffusion layer of soluble salts of poorly soluble basic drugs to improve dissolution performance. Mol Pharm. 2010;7:1441-9 pubmed publisher..Rotating disk dissolution data is presented which shows how these formulated solids can act to improve the dissolution profile for these materials. ..
- Flaherty A. Brain illness and creativity: mechanisms and treatment risks. Can J Psychiatry. 2011;56:132-43 pubmed..Art therapy and psychotherapy are not well studied. Preserving creative motivation can help creativity and other aspects of well-being in all patients, not just artists or researchers. ..
- Huang T, Fang F, Chen L, Zhu Y, Zhang J, Chen X, et al. Ginsenoside Rg1 attenuates oligomeric A?(1-42)-induced mitochondrial dysfunction. Curr Alzheimer Res. 2012;9:388-95 pubmed..This finding suggests that ginsenoside Rg1 may attenuate A?-induced neuronal death through the suppression of intracellular mitochondrial oxidative stress and may rescue neurons in AD. ..
- Briot K. [Drug-induced osteoporosis]. Rev Prat. 2012;62:187-92 pubmed..Further studies are necessary to confirm bone deleterious effect of other treatments. ..
- Rossi D, Martorana F, Brambilla L. Implications of gliotransmission for the pharmacotherapy of CNS disorders. CNS Drugs. 2011;25:641-58 pubmed publisher..Agents that are able to block the major steps of tumour necrosis factor-? and prostaglandin production and/or signalling can be proposed as novel therapeutic targets for the treatment of these disorders. ..
- Golubchik P, Sever J, Weizman A. [Efficacy and safety of stimulants and non-stimulants in adults with attention deficit hyperactivity disorder (ADHD)]. Harefuah. 2011;150:788-90, 814 pubmed..Methylphenidate treatment is recommended in cases when ADHD diagnosis was confirmed. Follow-up is required with special attention to possible cardiovascular, psychiatric and abusive side effects. ..
- Kumar B, Prakash A, Sewal R, Medhi B, Modi M. Drug therapy in autism: a present and future perspective. Pharmacol Rep. 2012;64:1291-304 pubmed..New classes of drugs with novel mechanisms of action should be there so that this disorder will become less prevalent in the future. ..
- Liu X, Petit J, Ezan P, Gyger J, Magistretti P, Giaume C. The psychostimulant modafinil enhances gap junctional communication in cortical astrocytes. Neuropharmacology. 2013;75:533-8 pubmed publisher..This article is part of the Special Issue Section entitled 'Current Pharmacology of Gap Junction Channels and Hemichannels'. ..
- Ablin J, Buskila D. Fibromyalgia syndrome--novel therapeutic targets. Maturitas. 2013;75:335-40 pubmed publisher..In the current review, current and emerging therapeutic options for the syndrome of fibromyalgia are covered. ..
- Beg S, Samad A, Alam M, Nazish I. Dendrimers as novel systems for delivery of neuropharmaceuticals to the brain. CNS Neurol Disord Drug Targets. 2011;10:576-88 pubmed..The present review should be of value to scientists who wish to work on the dendrimers for the delivery of molecules into the brain by systemic dosing. ..
- Hooshmandi Z, Rohani A, Eidi A, Fatahi Z, Golmanesh L, Sahraei H. Reduction of metabolic and behavioral signs of acute stress in male Wistar rats by saffron water extract and its constituent safranal. Pharm Biol. 2011;49:947-54 pubmed publisher..Moreover, the involvement of the amygdala in this observation can be ruled out. ..
- Kirilly E, Gonda X, Juhasz G, Bagdy G. [Anxiogenic and depressogenic side-effects of non-psychiatric drugs]. Orv Hetil. 2013;154:1327-36 pubmed publisher..Orv. Hetil., 2013, 154, 1327–1336. ..
- Li C, Lin G, Zuo Z. Pharmacological effects and pharmacokinetics properties of Radix Scutellariae and its bioactive flavones. Biopharm Drug Dispos. 2011;32:427-45 pubmed publisher..Moreover, due to abundant co-occurring bioactive components in Radix Scutellariae, our review further documents the pharmacokinetic interactions among them. ..
- Krieger D. Therapeutic drug approach to stimulate clinical recovery after brain injury. Front Neurol Neurosci. 2013;32:76-87 pubmed publisher..While factual repair of brain tissue may still be years away, research into the mechanisms of adaptation after brain injury offers more tangible return on the short run. ..
- Bamigboye J T, Josephine Y O, Olujide O O, A O, Shakir A M A, Mark R J E, et al. ISOLATION OF NOVEL PARA-PENTYL PHENYL BENZOATE FROM MONDIA WHITEI. (HOOK.F.) SKEELS (PERIPLOCACEAE), ITS STRUCTURE, SYNTHESIS AND NEUROPHARMACOLOGICAL EVALUATION. Afr J Tradit Complement Altern Med. 2017;14:219-230 pubmed publisher..These present data provide evidence for the role of para pentyl phenyl benzoate in the habitual consumption of the fruit as well as its central nervous system activities. ..
- Wise R, Preston C. What is the value of human FMRI in CNS drug development?. Drug Discov Today. 2010;15:973-80 pubmed publisher..An analysis of the value of FMRI to aid decision-making requires an appreciation of the techniques and their validation, a task that has begun and which necessitates an investment of its own. ..
- Kumar R, Sharma A, Saraf S, Gupta R. CNS activity of aqueous extract of root of Cissus quadrangularis Linn. (Vitaceae). J Diet Suppl. 2010;7:1-8 pubmed publisher..The extract also displayed prominent smooth muscle relaxant activity. The results suggest that the aqueous extracts of C. quadrangularis roots possess anticonvulsant, analgesic, and smooth muscle relaxant properties. ..
- Lee M, Rohn M, Tanda G, Leggio L. Targeting the Oxytocin System to Treat Addictive Disorders: Rationale and Progress to Date. CNS Drugs. 2016;30:109-23 pubmed publisher..This review summarizes the preclinical as well as clinical literature to date on the oxytocin system and its relevance to drug and alcohol addiction. ..
- Hamity M, White S, Hammond D. Effects of neurokinin-1 receptor agonism and antagonism in the rostral ventromedial medulla of rats with acute or persistent inflammatory nociception. Neuroscience. 2010;165:902-13 pubmed publisher..However, its actions are highly dependent on the stimulus modality and the type of injury, and this may be an additional basis for the poor efficacy of NK1 receptor antagonists in clinical trials. ..
- Geerts H, Spiros A, Roberts P, Carr R. Quantitative systems pharmacology as an extension of PK/PD modeling in CNS research and development. J Pharmacokinet Pharmacodyn. 2013;40:257-65 pubmed publisher..A powerful property is the ability to perform failure analysis. By giving examples from the CNS R&D field in schizophrenia and Alzheimer's disease, we will illustrate how this approach can make a difference for CNS R&D projects. ..
- Migdalska Richards A, Ko W, Li Q, Bezard E, Schapira A. Oral ambroxol increases brain glucocerebrosidase activity in a nonhuman primate. Synapse. 2017;71: pubmed publisher..We show that daily administration of ambroxol results in increased brain GCase activity. Our work further indicates that ambroxol should be investigated as a novel therapy for both PD and neuronopathic GD in humans. ..
- Tarcsay A, Nyíri K, Keseru G. Impact of lipophilic efficiency on compound quality. J Med Chem. 2012;55:1252-60 pubmed publisher..On the basis of the results reported here, monitoring lipophilic efficiency metrics could contribute significantly to compound quality and might improve the output of medicinal chemistry programs. ..
- Li X, Shen B, Zhuo X. [Application of liquid chromatography-high resolution mass spectrometry in toxicological screening]. Fa Yi Xue Za Zhi. 2011;27:376-81 pubmed..This review focuses on the applications of LC-HRMS in screening and identification of drug-of-abuse, prescription drugs, pesticide and stimulant. The prospect of LC-HRMS in forensic toxicology analysis is also included. ..
- Stranahan A, Arumugam T, Lee K, Mattson M. Mineralocorticoid receptor activation restores medial perforant path LTP in diabetic rats. Synapse. 2010;64:528-32 pubmed publisher..These results suggest additional mechanisms for diabetes-induced functional alterations and support a restorative role for dentate gyrus mineralocorticoid receptors. ..
- Alier K, Li Z, MacTavish D, Westaway D, Jhamandas J. Ionic mechanisms of action of prion protein fragment PrP(106-126) in rat basal forebrain neurons. J Neurosci Res. 2010;88:2217-27 pubmed publisher..These findings suggest novel links between PrP signalling partners inferred from genetic experiments, K(+) channels, and PrP-mediated neurotoxicity. ..
- Zong Y, Ai Q, Zhong L, Dai J, Yang P, He Y, et al. Ginsenoside Rg1 attenuates lipopolysaccharide-induced inflammatory responses via the phospholipase C-?1 signaling pathway in murine BV-2 microglial cells. Curr Med Chem. 2012;19:770-9 pubmed..This investigation demonstrates that Rg1 significantly attenuates overactivation of microglial cells by repressing expression levels of neurotoxic proinflammatory mediators and cytokines via activation of PLC-?1 signaling pathway. ..