Enhancement of long-term spatial memory in adult rats by the noncompetitive NMDA receptor antagonists, memantine and neramexane

Zoladz, Phillip R.; Campbell, Adam M.; Park, Collin R.; Schaefer, Daniela; Danysz, Wojciech; Diamond, David M.

doi:10.1016/j.pbb.2006.08.011

Cited by 112 publications

(68 citation statements)

References 67 publications

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“…Specifically, they found that memantine administered before three training sessions in the Morris water maze improved performance in a test given 24 h later. The results of Zoladz et al (2006) and the present study are unique because memantine improved memory in the absence of pharmacologic, genetic, or neurosurgical induction of impairment. However, the effects of memantine on radial arm maze performance in our study occurred at 0.3 and 0.56 mg/kg, which are considerably lower than the 5 and 7.5 mg/kg doses employed by Zoladz et al (2006).…”

Section: Discussionmentioning

confidence: 59%

“…A recent report also found that memantine enhanced performance in healthy rats (Zoladz et al, 2006). Specifically, they found that memantine administered before three training sessions in the Morris water maze improved performance in a test given 24 h later.…”

Section: Discussionmentioning

confidence: 86%

“…In several preclinical studies, memantine enhanced performance in various animal models of AD, such as transgenic mice carrying mutated human APP or PS1 (App/PS1) genes (Minkeviciene et al, 2004), the APP23 model (Van Dam and De Deyn, 2006), intracerebral ventricular infusion of β amyloid protein (Yamada et al, 2005), and rats with entorinal cortex lesions (Zajaczkowski et al, 1996). In naïve animals, memantine failed to enhance (Minkeviciene et al, 2004;Woodruff-Pak et al, 2006;Zajaczkowski et al, 1997) or disrupted (Creeley et al, 2006) memory performance in some studies, but was reported to improve memory retention in healthy rats evaluated in a Morris water maze task (Zoladz et al, 2006). Given the observation that disturbances in spatial orientation are a hallmark symptom Communicating Author: Aron H. Lichtman,alichtma@vcu.edu,Phone: 804.828.8480,Fax: 804.828.2117.…”

Section: Introductionmentioning

confidence: 99%

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The uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist memantine prolongs spatial memory in a rat delayed radial-arm maze memory task

Wise

Lichtman

2007

European Journal of Pharmacology

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In the present study, we evaluated the effects of memantine in a delayed radial arm maze rat task, consisting of an acquisition phase followed 18 h later by a win-shift retrieval test. When administered 20 min before acquisition, memantine elicited an inverted U-shape dose-response relationship, with low doses (0.3 and 0.56 mg/kg) reducing the number of errors committed during the retrieval test, while high doses (3 and 10 mg/kg) disrupted maze running. Memantine given immediately after acquisition or 20 min before retrieval failed to affect performance. Co-administration of subthreshold doses of memantine with either the CB 1 receptor antagonist rimonabant or the acetylcholine esterase inhibitor donepezil failed to enhance performance. Thus, low doses of memantine enhance acquisition processes that lead to prolonged spatial memory.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist memantine prolongs spatial memory in a rat delayed radial-arm maze memory task

Wise

Lichtman

2007

European Journal of Pharmacology

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“…However, taking into account that in the brain areas mainly affected in AD NMDARs are mainly composed by GluN2A and GluN2B subunits, this last observation may not be so relevant for the action of this compound in AD. Neramexane, an uncompetitive antagonist of NMDARs, has shown to be as efficient as memantine in enhancing long-term spatial memory in adult rats, but at lower doses (Zoladz et al, 2006), suggesting that this antagonist may represent an interesting alternative to memantine. Furthermore, taking into account the fact that extrasynaptic NMDARs have been associated with excitotoxicity in AD (Hardingham and Bading, 2010) and that extrasynaptic NMDARs are mainly composed by GluN2B-containing NMDARs (Tovar and Westbrook, 1999;Petralia, 2012), the use of a selective GluN2B subunit antagonists might be an interesting strategy to prevent M A N U S C R I P T…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Dysfunctional synapse in Alzheimer's disease – A focus on NMDA receptors

Mota¹,

Ferreira²,

Rego³

2014

Neuropharmacology

164

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Alzheimer's disease (AD) is the most prevalent form of dementia in the elderly.Alterations capable of causing brain circuitry dysfunctions in AD may take several years to develop. Oligomeric amyloid-beta peptide (Aβ) plays a complex role in the molecular events that lead to progressive loss of function and eventually to neurodegeneration in this devastating disease. Moreover, N-methyl-D-aspartate (NMDA) receptors (NMDARs) activation has been recently implicated in AD-related synaptic dysfunction. Thus, in this review we focus on glutamatergic neurotransmission impairment and the changes in NMDAR regulation in AD, following the description on the role and location of NMDARs at pre-and post-synaptic sites under physiological conditions. In addition, considering that there is currently no effective ways to cure AD or stop its progression, we further discuss the relevance of NMDARs antagonists to prevent AD symptomatology. This review posits additional information on the role played by Aβ in AD and the importance of targeting the tripartite glutamatergic synapse in early asymptomatic and possible reversible stages of the disease through preventive and/or disease-modifying therapeutic strategies.

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“…The compound displays a similar pharmacokinetic and comparable clinical tolerability. It enhanced a long-term spatial (hippocampusdependent) memory in adult rats, thus it was concluded that may be helpful in treatment of dementia [251].…”

Section: Neramexanementioning

confidence: 96%

Ion Channels as Drug Targets in Central Nervous System Disorders

Waszkielewicz¹,

Gunia²,

Szkaradek³

et al. 2013

CMC

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Ion channel targeted drugs have always been related with either the central nervous system (CNS), the peripheral nervous system, or the cardiovascular system. Within the CNS, basic indications of drugs are: sleep disorders, anxiety, epilepsy, pain, etc. However, traditional channel blockers have multiple adverse events, mainly due to low specificity of mechanism of action. Lately, novel ion channel subtypes have been discovered, which gives premises to drug discovery process led towards specific channel subtypes. An example is Na + channels, whose subtypes 1.3 and 1.7-1.9 are responsible for pain, and 1.1 and 1.2 -for epilepsy. Moreover, new drug candidates have been recognized. This review is focusing on ion channels subtypes, which play a significant role in current drug discovery and development process. The knowledge on channel subtypes has developed rapidly, giving new nomenclatures of ion channels. For example, Ca 2+ channels are not any more divided to T, L, N, P/Q, and R, but they are described as Ca v 1.1-Ca v 3.3, with even newer nomenclature 1A-1I and 1S. Moreover, new channels such as P2X1-P2X7, as well as TRPA1-TRPV1 have been discovered, giving premises for new types of analgesic drugs.

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Enhancement of long-term spatial memory in adult rats by the noncompetitive NMDA receptor antagonists, memantine and neramexane

Cited by 112 publications

References 67 publications

The uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist memantine prolongs spatial memory in a rat delayed radial-arm maze memory task

The uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist memantine prolongs spatial memory in a rat delayed radial-arm maze memory task

Dysfunctional synapse in Alzheimer's disease – A focus on NMDA receptors

Ion Channels as Drug Targets in Central Nervous System Disorders

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