The effect of eliprodil on the evolution of a focal cerebral ischaemia in vivo

Ibarrola, Danielle; Seegers, Hélène C.; Jaillard, Assia; Hommel, Marc; Décorps, M.; Massarelli, R.

doi:10.1016/s0014-2999(98)00330-6

Cited by 6 publications

(3 citation statements)

References 33 publications

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“…In preclinical studies, eliprodil had neuroprotective effects at 1 mg/kg (4,40,41). This corresponds to full ($99.5%) receptor occupancy in our study.…”

Section: Discussionsupporting

confidence: 64%

Evaluation of¹¹C-Me-NB1 as a Potential PET Radioligand for Measuring GluN2B-Containing NMDA Receptors, Drug Occupancy, and Receptor Cross Talk

Krämer

Betzel

et al. 2017

J Nucl Med

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Clinical and preclinical research with modulators at the -methyl-d-aspartate (NMDA) receptor GluN2B N-terminal domain (NTD) aims for the treatment of various neurologic diseases. The interpretation of the results is hampered by the lack of a suitable NMDA PET tracer for assessing the receptor occupancy of potential drugs. We have developedC-Me-NB1 as a PET tracer for imaging GluN1/GluN2B-containing NMDA receptors and used it to investigate in rats the dose-dependent receptor occupancy of eliprodil, a GluN2B NTD modulator. C-Me-NB1 was synthesized and characterized by in vitro displacement binding experiments with rat brain membranes, in vitro autoradiography, and blocking and displacement experiments by PET and PET kinetic modeling. Receptor occupancy by eliprodil was studied by PET withC-Me-NB1. C-Me-NB1 was synthesized at 290 ± 90 GBq/μmol molar activity, 7.4 ± 1.9 GBq total activity at the end of synthesis ( = 17), and more than 99% radiochemical purity. C-Me-NB1 binding in rat brain was blocked in vitro and in vivo by the NTD modulators Ro-25-6981 and eliprodil. Half-maximal receptor occupancy by eliprodil occurred at 1.5 μg/kg. At 1 mg/kg of eliprodil, a dose with reported neuroprotective effects, more than 99.5% of binding sites were occupied. In vitro,C-Me-NB1 binding was independent of the σ-1 receptor (Sigma1R), and the Sigma1R agonist (+)-pentazocine did not compete for high-affinity binding. In vivo, a 2.5 mg/kg dose of (+)-pentazocine abolished C-Me-NB1-specific binding, indicating an indirect effect of Sigma1R onC-Me-NB1 binding. C-Me-NB1 is suitable for the in vivo imaging of NMDA GluN1/GluN2B receptors and the assessment of receptor occupancy by NTD modulators. GluN1/GluN2B NMDA receptors are fully occupied at neuroprotective doses of eliprodil. Furthermore,C-Me-NB1 enables imaging of GluN1/GluN2B NMDA receptor cross talk.

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“…In preclinical studies, eliprodil had neuroprotective effects at 1 mg/kg (4,40,41). This corresponds to full ($99.5%) receptor occupancy in our study.…”

Section: Discussionsupporting

confidence: 64%

Evaluation of¹¹C-Me-NB1 as a Potential PET Radioligand for Measuring GluN2B-Containing NMDA Receptors, Drug Occupancy, and Receptor Cross Talk

Krämer

Betzel

et al. 2017

J Nucl Med

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“…A hyperacute lesion seen with DWI does not necessarily indicate infarction, because early cellular changes of ischemia (eg, cytotoxic edema) may potentially be reversed and lesion growth may be attenuated by reperfusion or neuroprotective drugs. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] Human studies of stroke with DWI and perfusion MRI have confirmed the ability of these methodologies to detect early ischemic lesions. 40 -47 Correlations of initial lesion volume by DWI to final infarct size on T2-weighted MRI have been observed, as have correlations of acute lesion volumes by DWI and chronic lesion volumes by T2-weighted imaging to scores of stroke clinical severity scales.…”

mentioning

confidence: 99%

Effect of citicoline on ischemic lesions as measured by diffusion‐weighted magnetic resonance imaging

Warach

Pettigrew

Dashe

et al. 2000

Annals of Neurology

211

128

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“…Despite the fact that animal studies have identified several strategies for stroke improvement, there is a lack of translation from preclinical to clinical trials. Although several attempts have been made to investigate the efficacy of behavior testing in animal models of white matter injury [ 73 ] and rodent models of stroke [ 74 ], some even measuring the validity and reliability of neurological scores in mice [ 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 ], all have generated conflicting results.…”

Section: Discussionmentioning

confidence: 99%

A Preclinical Systematic Review and Meta-Analysis of Behavior Testing in Mice Models of Ischemic Stroke

Boboc

Rotaru-Zavaleanu

Calina

et al. 2023

Life

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Stroke remains one of the most important causes of death and disability. Preclinical research is a powerful tool for understanding the molecular and cellular response to stroke. However, a lack of standardization in animal evaluation does not always ensure reproducible results. In the present study, we wanted to identify the best strategy for evaluating animal behavior post-experimental stroke. As such, a meta-analysis was made, evaluating behavioral tests done on male C57BL/6 mice subjected to stroke or sham surgery. Overall, fifty-six studies were included. Our results suggest that different types of tests should be used depending on the post-stroke period one needs to analyze. In the hyper-acute, post-stroke period, the best quantifier will be animal examination scoring, as it is a fast and inexpensive way to identify differences between groups. When evaluating stoke mice in the acute phase, a mix of animal examination and motor tests that focus on movement asymmetry (foot-fault and cylinder testing) seem to have the best chance of picking up differences between groups. Complex tasks (the rotarod test and Morris water maze) should be used within the chronic phase to evaluate differences between the late-subacute and chronic phases.

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The effect of eliprodil on the evolution of a focal cerebral ischaemia in vivo

Cited by 6 publications

References 33 publications

Evaluation of¹¹C-Me-NB1 as a Potential PET Radioligand for Measuring GluN2B-Containing NMDA Receptors, Drug Occupancy, and Receptor Cross Talk

Evaluation of¹¹C-Me-NB1 as a Potential PET Radioligand for Measuring GluN2B-Containing NMDA Receptors, Drug Occupancy, and Receptor Cross Talk

Effect of citicoline on ischemic lesions as measured by diffusion‐weighted magnetic resonance imaging

A Preclinical Systematic Review and Meta-Analysis of Behavior Testing in Mice Models of Ischemic Stroke

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The effect of eliprodil on the evolution of a focal cerebral ischaemia in vivo

Cited by 6 publications

References 33 publications

Evaluation of11C-Me-NB1 as a Potential PET Radioligand for Measuring GluN2B-Containing NMDA Receptors, Drug Occupancy, and Receptor Cross Talk

Evaluation of11C-Me-NB1 as a Potential PET Radioligand for Measuring GluN2B-Containing NMDA Receptors, Drug Occupancy, and Receptor Cross Talk

Effect of citicoline on ischemic lesions as measured by diffusion‐weighted magnetic resonance imaging

A Preclinical Systematic Review and Meta-Analysis of Behavior Testing in Mice Models of Ischemic Stroke

Contact Info

Product

Resources

About

Evaluation of¹¹C-Me-NB1 as a Potential PET Radioligand for Measuring GluN2B-Containing NMDA Receptors, Drug Occupancy, and Receptor Cross Talk

Evaluation of¹¹C-Me-NB1 as a Potential PET Radioligand for Measuring GluN2B-Containing NMDA Receptors, Drug Occupancy, and Receptor Cross Talk