Ketamine acts as a non-competitive N-methyl-d-aspartate antagonist on frog spinal cord in vitro

Martín, David; Lodge, D

doi:10.1016/0028-3908(85)90128-5

Cited by 174 publications

(61 citation statements)

References 16 publications

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“…This is in keeping with its known actions as a noncompetitive NMDA antagonist (Martin and Lodge, 1985), with reports of synergistic activity with putative neuroprotective drugs (Chang et al, 2002), and with our findings for both nicotinamide (Macleod et al, 2004) and melatonin (Macleod et al, in press).…”

Section: Efficacy Of Fk506 In Experimental Strokesupporting

confidence: 93%

Systematic Review and Metaanalysis of the Efficacy of FK506 in Experimental Stroke

Macleod

O’Collins

Horky

et al. 2005

J Cereb Blood Flow Metab

162

136

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FK506 is a candidate drug for acute stroke. For such drugs, any decision to proceed to clinical trial should be based on a full and unbiased assessment of the animal data, and consideration should be given to the limitations of those data. Such an assessment should include not only the efficacy of a drug but also the in vivo characteristics and limits to that efficacy. Here we use systematic review and meta-analysis to assess the evidence for a protective effect of FK506 in animal models of stroke. In all, 29 studies were identified describing procedures involving 1759 animals. The point estimate for the effect of FK506 was a 31.3% (95% confidence interval 27.2% to 35.4%) improvement in outcome. Efficacy was higher with ketamine anaesthesia and temporary ischaemia and was lower in rats, in animals with comorbidities, and where outcome was measured as infarct size alone. Reported study quality was modest by clinical trial standards, and efficacy was lower in high-quality studies. These findings show a substantial efficacy for FK506 in experimental stroke, but raise concerns that our estimate of effect size might be too high because of factors such as study quality and possible publication bias.

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Section: Efficacy Of Fk506 In Experimental Strokesupporting

confidence: 93%

Systematic Review and Metaanalysis of the Efficacy of FK506 in Experimental Stroke

Macleod

O’Collins

Horky

et al. 2005

J Cereb Blood Flow Metab

162

136

View full text Add to dashboard Cite

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“…There is further evidence that impaired acquisition of this task may depend on NMDA receptor blockade: ketamine, a dissociative anaesthetic like phencyclidine (PCP) known to antagonize noncompetitively the effect of NMDA sensitive glutamate receptors (Anis etal., 1983;Martin and Lodge, 1985) as well as MK-801, a novel and highly specific NMDA receptor antagonist produced a similar perturbation in the same task following systemic administration (Hauber, 1988;Bischoff et al, 1988;Alessandri et al, 1988). The present finding suggests a critical role of striatal NMDA receptors in control of delayed alternation and supports the "prefrontal systems"--hypothesis.…”

Section: Discussionmentioning

confidence: 93%

Effects of intrastriatal blockade of glutamatergic transmission on the acquisition of T-maze and radial maze tasks

Hauber

Schmidt

1989

J. Neural Transmission

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Summary. Prefrontal cortex and neostriatum constituting the prefrontal system are connected by glutamatergic neurones. The involvement of this corticostriatal projection in control of maze performance of rats was investigated. Glutamatergic transmission mediated by N-methyl-D-aspartate (NMDA) receptors was blocked by intrastriatal injections of dl-2-amino-5-phosphonovaleric acid (AP-5) (50 nmole in 0.5 ILl). In experiment 1, intrastriatal AP-5 was found to increase the number of errors during acquisition of a delayed alternation task in a T-maze. In experiment 2, the effect of intrastriatal AP-5 on acquisition of different 8 arm maze tasks was investigated. AP-5 did not affect the number of reentries on spontaneous and reinforced alternation; pre-and postdelay errors on delayed alternation were not altered. Therefore, intrastriatal NMDA receptor blockade impairs acquisition of a delayed alternation in a Tmaze, while intrastriatal blockade of NMDA receptors does not affect acquisition of different 8 arm maze tasks. The impairment in the T-maze task appears not to be due to deficient acquisition of spatial information per se, since 8 arm maze performance is intact. Instead, repeated delays in the T-maze task seem to be the critical component that gives difficulties in acquisition. These difficulties in bridging successive temporal discontiguities were attributed to an increased susceptibility to external and internal interfering stimuli during delays. Thus, striatal NMDA receptors within the prefrontal system may be involved in correct response retention over the duration of delays.

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“…The hippocampus is more sensitive to NMDA than the spinal cord (Martin & Lodge, 1985;Wheatley & Collins, 1986), cerebellum (Garthwaite et al, 1986) and other cortical regions (Harrison & Simmonds, 1985;Surtees & Collins, 1985;Wong et al, 1986;Martin & Lodge, 1987), whether expressed in terms of absolute potency or as potency relative to excitatory amino acids acting at non-NMDA receptors. This greater sensitivity may be due to the particularly high density of NMDA receptors in the CA1 region of the hippocampus (Cotman et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

“…Harrison & Simmonds, 1985;Martin & Lodge, 1985;Wheatley & Collins, 1986); the mean apparant pA2 value was 5.21 + 0.04 (11).…”

Section: Effects Of Antagonistsmentioning

confidence: 99%

A quantitative study of the actions of excitatory amino acids and antagonists in rat hippocampal slices

Blake

Brown

Collingridge

1988

British J Pharmacology

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4 Similar amino acid-induced depolarizations were observed in slices of just the CA1 region or in whole slices bathed in tetrodotoxin. Isolated alvear fibres, however, were insensitive to the excitatory amino acids. 5 D-2-Amino-5-phosphonovalerate (APV, 50pM) selectively and reversibly antagonized responses induced by NMDA (apparent pA2 = 5.21). 6 Kynurenic acid (1 mM) reversibly depressed responses to the three agonists tested. The doseratios for antagonism of AMPA, kainate and quisqualate were 6.9, 5.6 and 4.6 respectively. 7 This preparation has a different sensitivity profile to agonists from those of previously reported preparations of spinal cord, neocortex and cerebellum. The greater sensitivity to NMDA may be due to the higher density of NMDA receptors in the hippocampus. The effects of the antagonists, APV and kynurenate, are similar to those found in other brain areas.

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Ketamine acts as a non-competitive N-methyl-d-aspartate antagonist on frog spinal cord in vitro

Cited by 174 publications

References 16 publications

Systematic Review and Metaanalysis of the Efficacy of FK506 in Experimental Stroke

Systematic Review and Metaanalysis of the Efficacy of FK506 in Experimental Stroke

Effects of intrastriatal blockade of glutamatergic transmission on the acquisition of T-maze and radial maze tasks

A quantitative study of the actions of excitatory amino acids and antagonists in rat hippocampal slices

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