Riluzole, a glutamate antagonist, enhances slow wave and REM sleep in rats

Stutzmann, Jean‐Marie; Lucas, M.; Blanchard, Jean‐Charles; Laduron, Pierre M.

doi:10.1016/0304-3940(88)90125-5

Cited by 35 publications

(13 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, previous studies have demonstrated that oral administration of riluzole, which inhibits the release of glutamate and antagonizes ionotropic glutamate receptors, increases slow-wave sleep in rats in a dose-dependent manner (Stutzmann et al 1988) and thalamic injection of DL-2-amino-5-phosphonopentanoic acid (APV), an NMDA receptor antagonist, increases dSWS and paradoxical sleep in cats (Juhasz et al 1990). Moreover, NMDA injection into the basal forebrain has been shown to increase wakefulness (Cape and Jones 2000).…”

Section: Improved Sleep Following Glycine Ingestionmentioning

confidence: 80%

Pharmacokinetics and cerebral distribution of glycine administered to rats

et al. 2011

View full text Add to dashboard Cite

High doses of glycine have been reported to improve negative schizophrenic symptoms, suggesting that ingested glycine activates glutamatergic transmission via N-methyl-D-aspartate (NMDA) receptors. However, the pharmacokinetics of administered glycine in the brain has not been evaluated. In the present study, the time- and dose-dependent distributions of administered glycine were investigated from a pharmacokinetic viewpoint. Whole-body autoradiography of radiolabeled glycine was performed, and time-concentration curves for glycine and serine in plasma, cerebrospinal fluid (CSF), and brain tissues were obtained. Furthermore, pharmacokinetic parameters were calculated. For a more detailed analysis, the amount of glycine uptake in the brain was evaluated using the brain uptake index method. Radiolabeled glycine was distributed among periventricular organs in the brain. Oral administration of 2 g/kg of glycine significantly elevated the CSF glycine concentration above the ED50 value for NMDA receptors. The glycine levels in CSF were 100 times lower than those in plasma. Glycine levels were elevated in brain tissue, but with a slower time-course than in CSF. Serine, a major metabolite of glycine, was elevated in plasma, CSF, and brain tissue. Glycine uptake in brain tissue increased in a dose-dependent manner. Time-concentration curves revealed that glycine was most likely transported via the blood-CSF barrier and activated NMDA receptors adjacent to the ventricles. The pharmacokinetic analysis and the brain uptake index for glycine suggested that glycine was transported into brain tissue by passive diffusion. These results provide further insight into the potential therapeutic applications of glycine.

show abstract

Section: Improved Sleep Following Glycine Ingestionmentioning

confidence: 80%

Pharmacokinetics and cerebral distribution of glycine administered to rats

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Riluzole enhanced slow wave and rapid eye movement sleep (0.5-8mg/Kg) [130]. Although it is of direct relevance to suppressing the glutamatergic system, the demonstration of anaesthetic properties at very high doses (i.e.…”

Section: Gabaergic Mechanismsmentioning

confidence: 99%

Riluzole, Neuroprotection and Amyotrophic Lateral Sclerosis

Cheah

Vucic²,

Krishnan³

et al. 2010

CMC

230

146

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is a universally fatal neurodegenerative disease of the human motor system. Aetiological mechanisms implicated in the development of ALS have been linked to the glutamatergic neurotransmitter system, with destruction of motor neurons triggered through excessive activation of glutamate receptors at the synaptic cleft. This 'excitotoxicity' theory of ALS gave rise to the development of therapeutic approaches and ultimately clinical trials involving riluzole, initially thought to act solely as an inhibitor of glutamate release. Subsequent effects of riluzole have been postulated to include indirect antagonism of glutamate receptors, in addition to inactivation of neuronal voltage-gated Na+ channels. Riluzole remains the only disease-modifying therapy available to patients with ALS. Despite having been clinically available since the mid-1990 s, the in vivo pharmacological targets of riluzole have been poorly defined. An improved understanding concerning the potential neuroprotective mechanisms of riluzole may unearth pathophysiological processes that mediate neurodegeneration in ALS. The present review summarises the known chemical and pharmacological properties of riluzole. The failure of other putative neuroprotective therapies to demonstrate positive treatment outcomes in this intractable disease will be reviewed. Finally, the hypothesis that Na+ conductances may be involved in the processes of neuronal and axonal degeneration in ALS will be explored.

show abstract

“…It is therefore of interest that other lines of evidence sug· gest that excitatory amino acid (EAA) systems may be involved in sleep regulation. Direct brain administra tion of EAA agonists and antagonists alters sleep-related electrophysiology (Armstrong-James and Fox 1988; Stutzmann et al 1988;Juhasz et al 1990;Milasius et al 1990). Glutamate-like immunoreactivity has been found in many hypothalamic nuclei (van den Pol 1991) and recent evidence (Cahill and Menaker 1989;Ohiet al 1991) suggests that EAAs serve as presynaptic trans mitters for the retinal input to the suprachiasmatic nuclei.…”

Section: Discussionmentioning

confidence: 99%

Ketamine Administration During Waking Increases Delta EEG Intensity in Rat Sleep

Feinberg

Campbell

1993

Neuropsychopharmacol

View full text Add to dashboard Cite

Kmnnine is known to increase the metabolic rate of limbic Min structures. We exploited this action to test a �thesis of the homeostatic model of delta sleep: that II increase in the waking metabolic rate of plastic IltUTOnJlI systems would increase delta electro tlttp halographic (EEG) intensity in subsequent IDll rapid-eye-movement (NREM) sleep. In separate aptriments, we gave intraperitoneal injections of fttmn ine to Sprague-Dawley rats of either 15, 25, or 50 .glkg (0.055, 0.091, 0.18 mmollkg) three times, at NiIiWd by Elsevier Science Publishing Co., Inc. incidence) increased significantly over control (saline injections) levels. The magnitude of this increase places it among the largest pharmacologically induced stimulations of delta sleep yet observed. The interpretation of this effect is complicated by the fact that ketamine produces widespread metabolic changes throughout the brain and it also acts on several receptor classes. However, since ketamine's major action is noncompetitive blockade of the cation channel gated by the N-methyl-D-aspartate receptor, our data join recent observations that suggest that excitatory amino acid receptor systems are involved in sleep regulation. [Neuropsychopharmacology 9:41-48, 1993J plitude of delta waves during NREM sleep. (Elsewhere, we have shown that the ontogenetic curves for human cortical metabolic rate and delta wave amplitude paral lel that for synaptic density; all three brain variables show a steep decline over late childhood and adoles cence [Feinberg et al. 1990b]. Although synaptic reor ganization [toward fewer but more effective synapses] is a major part of brain reorganization during the sec ond decade of life, we speculate that this is only one component of a process in which neurons lose relative equipotentiality and become "committed" to specifIc roles in neural networks. In this revised model, both delta amplitude and waking metabolic rate are propor tional to the number of uncommitted neurons [Fein berg et al. 1990a]).Deoxyglucose studies of the brain effects of keta mine and its structural analogs, l-(l-phenylcyclohexyl) piperidine (PCP) and MK-801, suggested a more direct, albeit limited test of the intensity hypothesis. These drugs increase glucose utilization in plastic structures in the rat brain (hippocampus, cingulate and entorhi nal cortex) and decrease uptake in sensory and other 0893-133X/93/$O.OO

show abstract

Riluzole, a glutamate antagonist, enhances slow wave and REM sleep in rats

Cited by 35 publications

References 12 publications

Pharmacokinetics and cerebral distribution of glycine administered to rats

Pharmacokinetics and cerebral distribution of glycine administered to rats

Riluzole, Neuroprotection and Amyotrophic Lateral Sclerosis

Ketamine Administration During Waking Increases Delta EEG Intensity in Rat Sleep

Contact Info

Product

Resources

About