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Neuroactive Compounds
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Neuroactive Compounds

A special issue of Molecules (ISSN 1420-3049).

Deadline for manuscript submissions: closed (31 December 2010) | Viewed by 85591

Special Issue Editor

Dr. Maurice Tangui

E-Mail Website
Guest Editor
INSERM U. 710, University of Montpellier 2, CEDEX 5, 34095 Montpellier, France
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Research in Neuroscience has never been so active, taking benefits from recent developments in functional imaging, molecular biology and transgenesis, or improvements in animals’ cognitive behavioral analyses. Paradoxically, validation of new therapeutic strategies and marketing of really innovative medicine against pathologies with major social issues like Alzheimer’s disease and related neurodegenerative disorders, ischemic insults, depression, or schizophrenia mark time and do not find way out in a near future. Drug development pipelines of pharmaceutical companies remain alarmingly empty.
This combined Special Issue of Molecules and Pharmaceuticals, on Neuroactive Compounds, will offer an unique forum to present the chemistry, pharmacology and therapeutic opportunities offered by new and innovative molecular series in all areas of neuropharmacology and neuroscience. I strongly encourage authors to submit papers for this special issue, within the scope of Molecules and Pharmaceuticals, and I hope that the fields covered will allow to rise our hopes in seeing soon the validation of breakthrough treatments in central pathologies of major concern.

Dr. Tangui Maurice
Guest Editor

Keywords

  • psychoactive drugs
  • neuroprotective agents
  • antidepressant
  • anxiolytics
  • anti-stress drugs
  • brain imaging tools
  • brain penetration
  • blood-brain barrier agents

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Related Special Issue

Published Papers (6 papers)

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Research

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539 KiB  
Article
The Effects of Co-Treatment of 9-cis-Retinoic Acid and 15-Deoxy-Δ (12,14)-prostaglandin J2 on Microglial Activation
by Pei-Chien Hsu, Huey-Jen Tsay, Thomas J. Montine and Feng-Shiun Shie
Molecules 2011, 16(5), 4045-4058; https://doi.org/10.3390/molecules16054045 - 17 May 2011
Cited by 1 | Viewed by 6214
Abstract
Microglial activation plays an important role in the regulation of neuronal function and contributes to the development of neurodegeneration in Alzheimer’s disease (AD). Activation of nuclear peroxisome proliferator-activated receptor gamma (PPARγ) by an endogenous agonist, 15-deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2), has been shown to be [...] Read more.
Microglial activation plays an important role in the regulation of neuronal function and contributes to the development of neurodegeneration in Alzheimer’s disease (AD). Activation of nuclear peroxisome proliferator-activated receptor gamma (PPARγ) by an endogenous agonist, 15-deoxy-Δ(12,14)-prostaglandin J2 (15d-PGJ2), has been shown to be beneficial in many diseases with aberrant immune responses. Here, we report that co-treatment with 15d-PGJ2 and its synergistic partner, 9-cis-retinoic acid (RA), may modulate, but not abolish, microglial immune response activated by β-amyloid (Aβ) and interferon gamma (IFNγ). The co-treatment of RA and 15d-PGJ2 inhibited Aβ/IFNγ-activated immune response in primary microglia, as evidenced by suppressed expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2); and the effect was not affected by treatment with a PPARγ antagonist, GW9662. Data suggest that PPARγ activation may not contribute to the anti-inflammatory properties of the co-treatment. The co-treatment promoted microglial Aβ clearance in cultures; and the effect can be prevented by blocking PPARγ activation using GW9662. The effects of the co-treatment on Aβ clearance may be PPARγ-dependent. Intriguingly, secretion of microglial pro-nerve growth factor (pro-NGF) was inhibited by Aβ/IFNg treatment in a dose-dependent manner, suggesting that secretion of microglial pro-NGF may not contribute to the Ab/IFNg-activated microglial immune response. Taken together, the co-treatment may be beneficial for AD therapy; however, our data suggest that multiple mechanisms may underlie the beneficial effects of the co-treatment and are not limited to PPARγ activation only. Full article
(This article belongs to the Special Issue Neuroactive Compounds)
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Review

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216 KiB  
Review
Essential Oils and Their Constituents: Anticonvulsant Activity
by Reinaldo Nóbrega de Almeida, Maria de Fátima Agra, Flávia Negromonte Souto Maior and Damião Pergentino De Sousa
Molecules 2011, 16(3), 2726-2742; https://doi.org/10.3390/molecules16032726 - 23 Mar 2011
Cited by 109 | Viewed by 13561
Abstract
A literature-based survey of plants species and their essential oils with anticonvulsant activity was carried out. As results, 30 species belonging to 13 families and 23 genera were identified for their activities in the experimental models used for anticonvulsant drug screening. Thirty chemical [...] Read more.
A literature-based survey of plants species and their essential oils with anticonvulsant activity was carried out. As results, 30 species belonging to 13 families and 23 genera were identified for their activities in the experimental models used for anticonvulsant drug screening. Thirty chemical constituents of essential oils with anticonvulsant properties were described. Information on these 30 species is presented together with isolated bioactive compound studies. Full article
(This article belongs to the Special Issue Neuroactive Compounds)
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280 KiB  
Review
Analgesic-like Activity of Essential Oils Constituents
by Damião Pergentino De Sousa
Molecules 2011, 16(3), 2233-2252; https://doi.org/10.3390/molecules16032233 - 7 Mar 2011
Cited by 155 | Viewed by 20753
Abstract
Research on neuroactive drugs is a pharmaceutical sector of high interest and growth. The discovery of efficient drugs that can relieve pain is a subject of research in the pharmaceutical industry and academic field because pain is a symptom of many diseases. This [...] Read more.
Research on neuroactive drugs is a pharmaceutical sector of high interest and growth. The discovery of efficient drugs that can relieve pain is a subject of research in the pharmaceutical industry and academic field because pain is a symptom of many diseases. This review will summarize results on the discovery of essential oil constituents with analgesic-like activity from the chemical and pharmacological perspectives. Overall, 43 bioactive compounds were selected in nociception models. Among them, 62.8% were monoterpenes, 18.6% sesquiterpenes and other constituents represented 18.6%. The data show the potential of this group of natural product chemicals as analgesic drugs that may be useful for therapeutic purposes. Full article
(This article belongs to the Special Issue Neuroactive Compounds)
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122 KiB  
Review
Positive Allosteric Modulators of Type 5 Metabotropic Glutamate Receptors (mGluR5) and Their Therapeutic Potential for the Treatment of CNS Disorders
by Richard M. Cleva and M. Foster Olive
Molecules 2011, 16(3), 2097-2106; https://doi.org/10.3390/molecules16032097 - 2 Mar 2011
Cited by 64 | Viewed by 10261
Abstract
Studies utilizing selective pharmacological antagonists or targeted gene deletion have demonstrated thattype 5 metabotropic glutamate receptors (mGluR5) are critical mediators and potential therapeutic targets for the treatment of numerous disorders of the central nervous system (CNS), including depression, anxiety, drug addiction, chronic pain, [...] Read more.
Studies utilizing selective pharmacological antagonists or targeted gene deletion have demonstrated thattype 5 metabotropic glutamate receptors (mGluR5) are critical mediators and potential therapeutic targets for the treatment of numerous disorders of the central nervous system (CNS), including depression, anxiety, drug addiction, chronic pain, Fragile X syndrome, Parkinson’s disease, and gastroesophageal reflux disease. However, in recent years, the development of positive allosteric modulators (PAMs) of the mGluR5 receptor have revealed that allosteric activation of this receptor may also be of potential therapeutic benefit for the treatment of other CNS disorders, including schizophrenia, cognitive deficits associated with chronic drug use, and deficits in extinction learning. Here we summarize the discovery and characterization of various mGluR5 PAMs, with an emphasis on those that are systemically active. We will also review animal studies showing that these molecules have potential efficacy as novel antipsychotic agents. Finally, we will summarize findings that suggest that mGluR5 PAMs have pro-cognitive effects such as the ability toenhance synaptic plasticity, improve performance in various learning and memory tasks, including extinction of drug-seeking behavior, and reverse cognitive deficits produced by chronic drug use. Full article
(This article belongs to the Special Issue Neuroactive Compounds)
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140 KiB  
Review
Flavonoids and the CNS
by Anna K. Jäger and Lasse Saaby
Molecules 2011, 16(2), 1471-1485; https://doi.org/10.3390/molecules16021471 - 10 Feb 2011
Cited by 291 | Viewed by 21385
Abstract
Flavonoids are present in almost all terrestrial plants, where they provide UV-protection and colour. Flavonoids have a fused ring system consisting of an aromatic ring and a benzopyran ring with a phenyl substituent. The flavonoids can be divided into several classes depending on [...] Read more.
Flavonoids are present in almost all terrestrial plants, where they provide UV-protection and colour. Flavonoids have a fused ring system consisting of an aromatic ring and a benzopyran ring with a phenyl substituent. The flavonoids can be divided into several classes depending on their structure. Flavonoids are present in food and medicinal plants and are thus consumed by humans. They are found in plants as glycosides. Before oral absorption, flavonoids undergo deglycosylation either by lactase phloridzin hydrolase or cytosolic β-glucocidase. The absorbed aglycone is then conjugated by methylation, sulphatation or glucuronidation. Both the aglycones and the conjugates can pass the blood-brain barrier. In the CNS several flavones bind to the benzodiazepine site on the GABAA-receptor resulting in sedation, anxiolytic or anti-convulsive effects. Flavonoids of several classes are inhibitors of monoamine oxidase A or B, thereby working as anti-depressants or to improve the conditions of Parkinson’s patients. Flavanols, flavanones and anthocyanidins have protective effects preventing inflammatory processes leading to nerve injury. Flavonoids seem capable of influencing health and mood. Full article
(This article belongs to the Special Issue Neuroactive Compounds)
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166 KiB  
Review
Emerging Biological Importance of Central Nervous System Lanthionines
by Kenneth Hensley, Kalina Venkova and Alexandar Christov
Molecules 2010, 15(8), 5581-5594; https://doi.org/10.3390/molecules15085581 - 13 Aug 2010
Cited by 61 | Viewed by 12558
Abstract
Lanthionine (Lan), the thioether analog of cystine, is a natural but nonproteogenic amino acid thought to form naturally in mammals through promiscuous reactivity of the transsulfuration enzyme cystathionine-b-synthase (CbS). Lanthionine exists at appreciable concentrations in mammalian brain, where it undergoes aminotransferase conversion to [...] Read more.
Lanthionine (Lan), the thioether analog of cystine, is a natural but nonproteogenic amino acid thought to form naturally in mammals through promiscuous reactivity of the transsulfuration enzyme cystathionine-b-synthase (CbS). Lanthionine exists at appreciable concentrations in mammalian brain, where it undergoes aminotransferase conversion to yield an unusual cyclic thioether, lanthionine ketimine (LK; 2H-1,4-thiazine-5,6-dihydro-3,5-dicarboxylic acid). Recently, LK was discovered to possess neuroprotective, neuritigenic and anti-inflammatory activities. Moreover, both LK and the ubiquitous redox regulator glutathione (g-glutamyl-cysteine-glycine) bind to mammalian lanthionine synthetase-like protein-1 (LanCL1) protein which, along with its homolog LanCL2, has been associated with important physiological processes including signal transduction and insulin sensitization. These findings begin to suggest that Lan and its downstream metabolites may be physiologically important substances rather than mere metabolic waste. This review summarizes the current state of knowledge about lanthionyl metabolites with emphasis on their possible relationships to LanCL1/2 proteins and glutathione. The potential significance of lanthionines in paracrine signaling is discussed with reference to opportunities for utilizing bioavailable pro-drug derivatives of these compounds as novel pharmacophores. Full article
(This article belongs to the Special Issue Neuroactive Compounds)
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