scholarly journals Memantine as an Augmentation Therapy for Anxiety Disorders

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Thomas L. Schwartz ◽  
Umar A. Siddiqui ◽  
Shafi Raza
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nmda Receptor ◽  
Adverse Events ◽  
Nmda Receptor Antagonist ◽  
Augmentation Therapy ◽  
Treatment Resistant ◽  
Excitatory Neurotransmitter ◽  
The Central Nervous System ◽  
Development Of Anxiety

Objective. Glutamate, an excitatory neurotransmitter in the central nervous system (CNS), may play a role in the development of anxiety. Memantine partially blocks N-methyl-D-aspartate (NMDA) receptors' glutamate channels located in the CNS. This paper evaluates memantine as an augmentation therapy for treatment of anxiety.Methods. 15 consecutive partially responding anxious patients were treated with adjunctive memantine for 10 weeks. Memantine was dosed 5–20 mg/day.Result. Memantine augmentation resulted in clinically relevant reduction in anxiety symptoms when compared to baseline. Forty percent of patients achieved remission (HAM-A ≥ 7). Memantine improved sleep quality. Mean dose was 14 mg/d (range 5–20 mg/d). Typical adverse events included nausea and headache.Conclusion. The NMDA receptor antagonist memantine may be an effective augmentation therapy in patients with treatment-resistant anxiety.

scholarly journals Mechanisms of Glutamate Transport

2013 ◽  
Vol 93 (4) ◽  
pp. 1621-1657 ◽  
Author(s):  
Robert J. Vandenberg ◽  
Renae M. Ryan
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Glutamate Transporter ◽  
Glutamate Transporters ◽  
Structural Basis ◽  
Broad Perspective ◽  
Excitatory Neurotransmitter ◽  
Brain Functions ◽  
Transporter Family ◽  
The Central Nervous System

l-Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system and plays important roles in a wide variety of brain functions, but it is also a key player in the pathogenesis of many neurological disorders. The control of glutamate concentrations is critical to the normal functioning of the central nervous system, and in this review we discuss how glutamate transporters regulate glutamate concentrations to maintain dynamic signaling mechanisms between neurons. In 2004, the crystal structure of a prokaryotic homolog of the mammalian glutamate transporter family of proteins was crystallized and its structure determined. This has paved the way for a better understanding of the structural basis for glutamate transporter function. In this review we provide a broad perspective of this field of research, but focus primarily on the more recent studies with a particular emphasis on how our understanding of the structure of glutamate transporters has generated new insights.

scholarly journals Ixekizumab for patients with plaque psoriasis affected by multiple sclerosis

2021 ◽  
Author(s):  
Enrique Herrera-Acosta ◽  
Gustavo Guillermo Garriga Martina ◽  
Jorge Alonso Suárez-Pérez ◽  
Eliseo Alejandro Martínez-García ◽  
Enrique Herrera-Ceballos
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Monoclonal Antibody ◽  
Nervous System ◽  
Adverse Events ◽  
Plaque Psoriasis ◽  
Neurological Disease ◽  
Chronic Plaque Psoriasis ◽  
Demyelinating Disorder ◽  
The Central Nervous System

Multiple sclerosis is an autoimmune demyelinating disorder of the central nervous system that shares similar immunopathogenic mechanisms with chronic plaque psoriasis, such as the overexpression of the Th17 pathway. We report the case of a patient with multiple sclerosis and severe chronic plaque psoriasis successfully treated with ixekizumab (anti IL-17A and IL-17A/F monoclonal antibody). The treatment achieved a complete skin clearance (PASI 100 response) with no adverse events or evidence of progression of the neurological disease. Keywords: Psoriasis; Ixekizumab; Multiple sclerosis

Evaluation of safety and side effects in the process of anti-anxiety drug development *

1993 ◽  
Vol 8 (6) ◽  
pp. 285-291 ◽  
Author(s):  
M Bourin ◽  
A Couetoux du Tertre ◽  
R Payeur
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Side Effects ◽  
Adverse Events ◽  
Vital Signs ◽  
The Elderly ◽  
System Level ◽  
The Central Nervous System ◽  
Drug Type ◽  
Central Nervous System Level

SummaryAs with other drugs it is necessary to look for changes induced by anxiolytics on vital signs, laboratory parameters and adverse events. In return, in a more specific way for anxiolytics, we will look at side effects at the central nervous system level with psychological and physiological battery tests. We will also assess the safety of use of anxiolytics in certain specific conditions, such as overdose or withdrawal and in certain populations such as the elderly, neonates and children. The assessment of safety and side effects, whatever the drug type studied, must come early in the developing process of a drug (phases I, II and III).

scholarly journals Molecular biology of the apteronotus NMDA receptor NR1 subunit

1999 ◽  
Vol 202 (10) ◽  
pp. 1319-1326
Author(s):  
R.J. Dunn ◽  
D. Bottai ◽  
L. Maler
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nmda Receptor ◽  
Alternative Splice ◽  
Expression Patterns ◽  
Pyramidal Cells ◽  
Weakly Electric Fish ◽  
Hybridization Technique ◽  
The Central Nervous System ◽  
Splice Isoform

The complete sequences and expression patterns of the NR1 (aptNR1) subunit of the N-methyl-d-aspartate (NMDA) receptor and its alternative splice isoforms have been determined for the weakly electric fish Apteronotus leptorhynchus. The deduced amino acid sequence of aptNR1 is approximately 88 % identical to the NR1 sequences of other vertebrate. Two of the three alternative splice cassettes previously described for mammalian NR1s, N1 and C1, are present in aptNR1, but the third cassette, C2, is not found. In addition, two teleost-specific splice cassettes occur on the N-terminal side of the C1 sequence. The cellular patterns of aptNR1 expression, including the patterns of N1 and C1 splicing, have been mapped using the in situ hybridization technique. High levels of aptNR1 mRNA were detected throughout the central nervous system including most neurons of the electrosensory system, with the highest levels in electrosensory lateral line lobe pyramidal cells. Expression of the N1 splice isoform was higher in more caudal regions of the brain, and expression of the C1 splice isoform was higher in more rostral regions. The N1 splice isoform was present in almost all NR1-positive cells, in contrast to the C1 splice isoform which was restricted to a subset of NR1-positive cells. These results demonstrate that the NR1 subunit of the NMDA receptor is evolutionarily conserved across species and that regulation of alternative RNA splicing modulates the properties of NR1 in different neurons of the central nervous system of A. leptorhynchus.

Fast Analytical Sensing Technology: Microelectrode-Based Recordings of Tonic and Phasic Neurotransmitter Signalling in the Mammalian Brain

2018 ◽  
pp. 500-510
Author(s):  
Michelle L. Humeiden ◽  
Jorge E. Quintero ◽  
John T. Slevin ◽  
Greg A. Gerhardt
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Clinical Applications ◽  
Mammalian Brain ◽  
Excitatory Neurotransmitter ◽  
Ideal Candidate ◽  
Ca1 Region ◽  
Sensing Technology ◽  
The Central Nervous System ◽  
The Brain

Communication in the nervous system is predominately chemical. However, understanding of neurotransmitter signalling in normal and diseased states remains lacking. Electrochemically based biosensors can detect chemical messengers on a near-real timescale, allowing exploration of neurotransmitter systems to bring into focus the functioning elements of this critical means of communication. Glutamate, the predominant excitatory neurotransmitter of the central nervous system, is an ideal candidate for measurement with biosensors. With biosensors, it has been found that spontaneous glutamate signals in the dentate gyrus are enhanced in kindled animals. Meanwhile, in a model of epilepsy, the utility of detecting and the dynamism of glutamate signalling become apparent as tonic glutamate levels and rapid, spontaneous phasic glutamate signals show a correlation with seizure activity in the CA1 region of rodents. The ability of these biosensors to detect neurotransmitters in the brain is promising for clinical applications to monitor and, eventually, treat epilepsy.

scholarly journals Excitatory Amino Acid Transporters in Physiology and Disorders of the Central Nervous System

2019 ◽  
Vol 20 (22) ◽  
pp. 5671 ◽  
Author(s):  
Malik ◽  
Willnow
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Amino Acid ◽  
Chloride Channels ◽  
Excitatory Amino Acid ◽  
Amino Acid Transporters ◽  
Excitatory Amino Acid Transporters ◽  
Excitatory Neurotransmitter ◽  
Cerebellar Ataxias ◽  
The Central Nervous System

Excitatory amino acid transporters (EAATs) encompass a class of five transporters with distinct expression in neurons and glia of the central nervous system (CNS). EAATs are mainly recognized for their role in uptake of the amino acid glutamate, the major excitatory neurotransmitter. EAATs-mediated clearance of glutamate released by neurons is vital to maintain proper glutamatergic signalling and to prevent toxic accumulation of this amino acid in the extracellular space. In addition, some EAATs also act as chloride channels or mediate the uptake of cysteine, required to produce the reactive oxygen speciesscavenger glutathione. Given their central role in glutamate homeostasis in the brain, as well as their additional activities, it comes as no surprise that EAAT dysfunctions have been implicated in numerous acute or chronic diseases of the CNS, including ischemic stroke and epilepsy, cerebellar ataxias, amyotrophic lateral sclerosis, Alzheimer’s disease and Huntington’s disease. Here we review the studies in cellular and animal models, as well as in humans that highlight the roles of EAATs in the pathogenesis of these devastating disorders. We also discuss the mechanisms regulating EAATs expression and intracellular trafficking and new exciting possibilities to modulate EAATs and to provide neuroprotection in course of pathologies affecting the CNS.

scholarly journals Neurosarcoidosis Presentation as Adipsic Diabetes Insipidus Secondary to a Pituitary Stalk Lesion and Association with Anti-NMDA Receptor Antibodies

2020 ◽  
Vol 2020 ◽  
pp. 1-5 ◽  
Author(s):  
Jose Gabriel Solis ◽  
Arturo Olascoaga Lugo ◽  
Marco Antonio Rodríguez Florido ◽  
Bayron Alexander Sandoval Bonilla ◽  
Jose Malagón Rangel
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nmda Receptor ◽  
Diabetes Insipidus ◽  
Skin Lesions ◽  
Pituitary Mass ◽  
Atypical Symptoms ◽  
The Central Nervous System ◽  
Noncaseating Granulomas ◽  
Receptor Antibodies

Sarcoidosis is a multisystemic inflammatory disease of unknown cause. It is characterized by the presence of noncaseating granuloma on a biopsy specimen. Clinical presentation varies across case report series with myriad of symptoms ranging from fever, respiratory symptoms, and skin lesions, or atypical symptoms like heart block or neurological symptoms. Hence, we report the case of a 22-year-old woman with encephalitis, a pituitary mass, and adipsic diabetes insipidus. The diagnostic approach did not end on the biopsy of the lesion, which reported noncaseating granulomas; on the contrary, it was the beginning of a path to exclude other causes of the central nervous system granulomas that ended with the diagnosis of the isolated central nervous system sarcoidosis. Also, we report the first proven association between anti-NMDA receptor antibodies and sarcoidosis.

scholarly journals NMDA receptor modulation and severe acute respiratory syndrome treatment

F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 1060
Author(s):  
Blaise M. Costa
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nmda Receptor ◽  
Severe Acute Respiratory Syndrome ◽  
Synergetic Effect ◽  
Downstream Signaling ◽  
Receptor Modulation ◽  
Human Lungs ◽  
The Central Nervous System ◽  
Nervous System Function

N-Methyl-D-aspartate (NMDA) subtype of glutamate receptors is expressed in the human lungs and central nervous system.  NMDA receptor potentiation could increase calcium ion influx and promote downstream signaling mechanisms associated with cellular contractions that are disrupted in severe acute respiratory syndrome. Pharmacological effects generated by triggering glutamate receptor function in the brain, coupled with concurrent stimulation of the respiratory tract, may produce a synergetic effect, improving the airway smooth muscle function. A novel multipronged intervention to simultaneously potentiate NMDA receptors expressed both in the central nervous system and airway muscles would be helpful for the treatment of severe acute respiratory syndrome that deteriorates peripheral and central nervous system function before causing death in humans.

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