Antidepressant-like actions of the polyamine site NMDA antagonist, eliprodil (SL-82.0715)

Layer, Richard T.; Popik, Piotr; Olds, Tia; Skolnick, Phil

doi:10.1016/0091-3057(95)00155-p

Cited by 124 publications

(57 citation statements)

References 32 publications

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“…[12][13][14][15][16][17] A single dose of the NMDA antagonist ketamine hydrochloride in male Wistar rats interferes with the induction of behavioral despair for up to 10 days after its administration. 18 Additionally, repeated administration of different classes of antidepressants-in a time frame consistent with the delayed therapeutic effectsbrings about alterations in the expression of NMDA subunit messenger RNA 19 and radioligand binding to these receptors in regions of the brain implicated in the pathophysiology of depression.…”

Section: -11mentioning

confidence: 99%

A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression

Zarate

Singh²,

Carlson³

et al. 2006

Arch Gen Psychiatry

3,211

100

2,185

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Section: -11mentioning

confidence: 99%

A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression

Zarate

Singh²,

Carlson³

et al. 2006

Arch Gen Psychiatry

3,211

100

2,185

View full text Add to dashboard Cite

show abstract

“…12,24,80,[93][94][95][96][97][98][99] Berman et al 93 studied seven subjects with major depression who, in a double-blind placebocontrolled manner, received intravenous ketamine or saline with active and sham treatments separated by at least 1 week. They noted a significant reduction in Hamilton Depression Rating Scale scores within 72 h after ketamine but not placebo, with results lasting for nearly 1 week.…”

Section: Antidepressant Effects On Glutamatergic Neurotransmissionmentioning

confidence: 99%

Advances in the treatment of anxiety: Targeting glutamate

Simon

Gorman

2006

NeuroRX

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Our current psychopharmacological treatments for anxiety disorders evince a number of shortcomings, including troublesome side effects and lack of primary effects. Whereas many new drugs have been developed in the past few decades, most are based on outmoded theories of the pathogenesis of these disorders (i.e., monoamine hypotheses), thus frustrating our ability to create more specific and effective interventions. Recently, however, the neurobiological literature has shown a convergence of findings focusing on the glutamatergic system in anxiety disorders, and the growth of pharmacological tools targeting these receptors has led to the development of novel treatments having anxiolytic effects in humans and animals alike. Additionally, as this system is showing promise as a final common pathway in the pathogenesis of anxiety disorders, we may be able to employ glutamate-specific neuroimaging techniques (e.g., N-acetyl-aspartate, GLX) to both guide treatment decisions and present reliable objective biomarkers for treatment efficacy.

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“…Compounds that decrease glutamatergic transmission via blockade of ionotropic NMDA or group I metabotropic glutamate receptors produce antidepressant-like effect in animal screening procedures (Layer et al, 1995;Moryl et al, 1993;Papp and Moryl, 1994;Skolnick, 1999;Tatarczynska et al, 2001). Moreover, recent studies have revealed that agonists of group III metabotropic glutamate receptors, known to inhibit glutamate release, exhibit antidepressant-like activity in animals (Palucha et al, 2004;Tatarczynska et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Elevated Levels of the NR2C Subunit of the NMDA Receptor in the Locus Coeruleus in Depression

Karolewicz

Stockmeier

Ordway

2005

Neuropsychopharmacol

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Low levels of the intracellular mediator of glutamate receptor activation, neuronal nitric oxide synthase (nNOS) were previously observed in locus coeruleus (LC) from subjects diagnosed with major depression. This finding implicates abnormalities in glutamate signaling in depression. Receptors responding to glutamate in the LC include ionotropic N-methyl-D-aspartate receptors (NMDARs). The functional NMDAR is a hetero-oligomeric structure composed of NR1 and NR2 (A-D) subunits. Tissue containing the LC and a nonlimbic LC projection area (cerebellum) was obtained from 13 and 9 matched pairs, respectively, of depressed subjects and control subjects lacking major psychiatric diagnoses. NMDAR subunit composition in the LC was evaluated in a psychiatrically normal subject. NR1 and NR2C subunit immunoreactivities in LC homogenates showed prominent bands at 120 and 135 kDa, respectively. In contrast to NR1 and NR2C, very weak immunoreactivity of NR2A and NR2B subunits was observed in the LC. Possible changes in concentrations of NR1 and NR2C that might occur in depression were assessed in the LC and cerebellum. The overall amount of NR1 immunoreactivity was normal in the LC and cerebellum in depressed subjects. Amounts of NR2C protein were significantly higher ( þ 61%, p ¼ 0.003) in the LC and modestly, but not significantly, elevated in the cerebellum ( þ 35%) of depressives as compared to matched controls. Higher levels of NR2C subunit implicate altered glutamatergic input to the LC in depressive disorders.

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Antidepressant-like actions of the polyamine site NMDA antagonist, eliprodil (SL-82.0715)

Cited by 124 publications

References 32 publications

A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression

A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression

Advances in the treatment of anxiety: Targeting glutamate

Elevated Levels of the NR2C Subunit of the NMDA Receptor in the Locus Coeruleus in Depression

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