AProspective, Open-Label Trial of Memantine in the Treatment of Cognitive, Behavioral, and Memory Dysfunction in Pervasive Developmental Disorders

Owley, Thomas; Salt, Jeff; Guter, Stephen J.; Grieve, Adam; Walton, Laura; Ayuyao, Nelson; Leventhal, Bennett L.; Cook, Edwin H.

doi:10.1089/cap.2006.16.517

Cited by 105 publications

(62 citation statements)

References 13 publications

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“…Among them, memantine (Namenda) (Fig. 4E), previously well tolerated in a pediatric population, was selected for off-label use as a potentially effective antagonist of the mutant NMDA receptors (Owley et al, 2006;Chez et al, 2007;Erickson et al, 2007). Although only a single patient was examined, the addition of memantine to valproate treatment (see also Urbanska et al, 1992) nevertheless decreased the frequency of seizures from .11 per week to approximately three per Fig.…”

Section: Gaba/glutamate Receptor Mutations In Neurologic Diseasesmentioning

confidence: 99%

Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases

Yuan¹,

Low²,

Moody³

et al. 2015

Mol Pharmacol

186

176

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The advent of whole exome/genome sequencing and the technology-driven reduction in the cost of next-generation sequencing as well as the introduction of diagnostic-targeted sequencing chips have resulted in an unprecedented volume of data directly linking patient genomic variability to disorders of the brain. This information has the potential to transform our understanding of neurologic disorders by improving diagnoses, illuminating the molecular heterogeneity underlying diseases, and identifying new targets for therapeutic treatment. There is a strong history of mutations in GABA receptor genes being involved in neurologic diseases, particularly the epilepsies. In addition, a substantial number of variants and mutations have been found in GABA receptor genes in patients with autism, schizophrenia, and addiction, suggesting potential links between the GABA receptors and these conditions. A new and unexpected outcome from sequencing efforts has been the surprising number of mutations found in glutamate receptor subunits, with the GRIN2A gene encoding the GluN2A N-methyl-D-aspartate receptor subunit being most often affected. These mutations are associated with multiple neurologic conditions, for which seizure disorders comprise the largest group. The GluN2A subunit appears to be a locus for epilepsy, which holds important therapeutic implications. Virtually all a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor mutations, most of which occur within GRIA3, are from patients with intellectual disabilities, suggesting a link to this condition. Similarly, the most common phenotype for kainate receptor variants is intellectual disability. Herein, we summarize the current understanding of disease-associated mutations in ionotropic GABA and glutamate receptor families, and discuss implications regarding the identification of human mutations and treatment of neurologic diseases.

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Section: Gaba/glutamate Receptor Mutations In Neurologic Diseasesmentioning

confidence: 99%

Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases

Yuan¹,

Low²,

Moody³

et al. 2015

Mol Pharmacol

186

176

View full text Add to dashboard Cite

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“…As presented in Figure 1A-B, 3-minute-long ischemia almost completely destroyed the pyramidal neurons. This effect remained unchanged after the injection of memantine 24,48,72 and 96 h before the insult (Fig. 1A).…”

Section: Resultsmentioning

confidence: 84%

“…Memantine is widely used in adults for the treatment of dementia, particularly of the Alzheimer's type [49], and its safety has been demonstrated [63]. There have also been clinical tests evaluating the therapeutic potential of memantine in children diagnosed with developmental disorders including autism [10,48]. It appeared protective in the treatment of periventricular leukomalacia in a rat model [43] and neuroprotective in hypoxia-ischemia in PND7 rats [37].…”

Section: Discussionmentioning

confidence: 99%

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Original article Delayed preconditioning with NMDA receptor antagonists in a rat model of perinatal asphyxia

Makarewicz¹,

Sulejczak²,

Duszczyk³

et al. 2014

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A b s t r a c t Introduction: In vitro experiments have demonstrated that preconditioning primary neuronal cultures by temporary application of NMDA receptor antagonists induces long-term tolerance against lethal insults.In the present study we tested whether similar effects also occur in brain submitted to ischemia in vivo and whether the potential benefit outweighs the danger of enhancing the constitutive apoptosis in the developing brain. Material and methods: Memantine in pharmacologically relevant doses of 5 mg/kg or (+)MK-801 (3 mg/kg) was administered i.p. 24, 48, 72 and 96 h before 3-min global forebrain ischemia in adult Mongolian gerbils or prior to hypoxia/ ischemia in 7-day-old rats. Neuronal loss in the hippocampal CA1 in gerbils or weight deficit of the ischemic hemispheres in the rat pups was evaluated after 14 days. Also, the number of apoptotic neurons in the immature rat brain was evaluated. Results: In gerbils only the application of (+)MK-801 24 h before ischemia resulted in significant prevention of the loss of pyramidal neurons. In rat pups administration of (+)MK-801 at all studied times before hypoxia-ischemia

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“…87 Studies of memantine, an NMDA antagonist, have shown significant improvements in autism in at least two reported studies, with one study that had almost 200 patients. 88,89 These observations have led to memantine studies that are currently in progress with the potential hope of future clinical application in autism. Amantidine has also been studied as a potential treatment in autism, as it also acts on the NMDA receptor.…”

Section: Glutamate and Nmda Receptorsmentioning

confidence: 99%

Immune Therapy in Autism: Historical Experience and Future Directions with Immunomodulatory Therapy

Chez

Guido-Estrada

2010

Neurotherapeutics

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Summary: Autism affects 1 in 110 new births, and it has no single etiology with uniform agreement. This has a significant impact on the quality of life for individuals who have been diagnosed with autism. Although autism has a spectrum quality with a shared diagnosis, it presents a uniquely different clinical appearance in each individual. Recent research of suspected immunological factors have provided more support for a probable immunological process or for processes that may play a role in the acquisition of an autistic condition. These factors include prenatal, genetic, and postnatal findings, as well as the discovery of a dysfunctional chronic pro-inflammatory state in brain tissue and cerebrospinal fluid in subsets of autistic patients. These findings offer new theories that may lead to the development of disease modification or preventative therapeutic options in the near future. This article reviews prenatal, genetic, and observed immune aspects of the autism condition that may be risk factors in the presentation of the autistic clinical phenotype. Historical immune interventions in autism are reviewed and potential new therapies and interventions are discussed.

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AProspective, Open-Label Trial of Memantine in the Treatment of Cognitive, Behavioral, and Memory Dysfunction in Pervasive Developmental Disorders

Cited by 105 publications

References 13 publications

Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases

Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases

Original article Delayed preconditioning with NMDA receptor antagonists in a rat model of perinatal asphyxia

Immune Therapy in Autism: Historical Experience and Future Directions with Immunomodulatory Therapy

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