Acute Pharmacokinetics of Memantine in the Mouse

Saab, Bechara J.; Roder, John

doi:10.1159/000332829

Cited by 9 publications

(4 citation statements)

References 39 publications

(31 reference statements)

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“…injections of 5 mg/kg memantine selectively enhanced the behavioural performance of Ts65Dn mice in a fear conditioning test. Similar to previously published work in which memantine was injected subcutaneously (s.c.) in wild‐type mice , concentrations of memantine in plasma, brain and liver displayed a dose‐dependent linear growth (fig. ).…”

Section: Resultsmentioning

confidence: 99%

“…We have shown that the memantine distribution in plasma, brain and liver of Ts65Dn and euploid F1 hybrid mice in response to single i.p., acute administrations of increasing doses of this drug (2.5–40 mg/kg) follows a simple linear dose dependence. This is in agreement with previously reported work in which memantine was injected s.c. to wild‐type C57CL/6 mice . In that study, these authors observed that 10 mg/kg memantine s.c. produced a mean plasma concentration of 2.15 μmol/l 100 min.…”

Section: Discussionmentioning

confidence: 99%

“…There have been a few published methods for the determination of the concentration of memantine in blood and tissues [22][23][24][25][26][27][28][29]. Based on these published reports and our expertise, we developed a unique procedure for measuring memantine concentration in blood and tissues using commonly found GC/MS.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetic Properties of Memantine after a Single Intraperitoneal Administration and Multiple Oral Doses in Euploid Mice and in the Ts65Dn Mouse Model of Down's Syndrome

Victorino

Bederman

Costa

2017

Basic Clin Pharma Tox

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Memantine is a drug approved for the treatment of moderate-to-severe Alzheimer's disease (AD), and there is ongoing research on the potential expansion of its clinical applicability. Published data on the pharmacokinetics of memantine in the mouse are still incomplete, particularly for chronic administration regimens and mouse models of specific genetic disorders. Down's syndrome (DS) is a genetic disorder known to affect multiple organs and systems, with the potential to alter significantly drug pharmacokinetics. Here, we describe a simple, efficient and sensitive GC/MS-based procedure for the determination of memantine concentrations in murine blood and tissue samples. We analysed pharmacokinetic properties of memantine, particularly its distribution in blood, brain and liver in the Ts65Dn mouse model of DS and euploid F1 hybrid mice after single intraperitoneal administrations of increasing doses of this drug. We also determined steady-state memantine concentrations in plasma, brain and liver after chronic oral administration of this drug in adult male Ts65Dn mice, euploid littermate controls and nursing or pregnant Ts65Dn mice. Our results revalidated the acute dose of memantine used in previously published work, determined the appropriate amount of memantine to be mixed into mouse chow to achieve steady and pharmacologically relevant plasma and tissue levels of this drug and demonstrated that memantine can be transferred from mother to offspring via maternal milk and placenta. Most of these findings are potentially applicable not only to the study of DS but also to other neurodevelopmental and neurodegenerative disorders.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetic Properties of Memantine after a Single Intraperitoneal Administration and Multiple Oral Doses in Euploid Mice and in the Ts65Dn Mouse Model of Down's Syndrome

Victorino

Bederman

Costa

2017

Basic Clin Pharma Tox

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“…Rather, these data strongly suggest that memantine causes lasting alterations in glutamatergic synaptic transmission in the ventral hippocampus. In vivo, memantine remains in plasma for up to 132 h after oral administration [28] and can be detected in mouse brain 100 min after administration [29]. According to microdialysis data, the half-life of memantine in rodent brain is approximately 3 h [30].…”

Section: Ca1mentioning

confidence: 99%

Memantine Disrupts Motor Coordination through Anxiety-like Behavior in CD1 Mice

et al. 2022

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Memantine is an FDA approved drug for the treatment of Alzheimer’s disease. It reduces neurodegeneration in the hippocampus and cerebral cortex through the inhibition of extrasynaptic NMDA receptors in patients and mouse models. Potentially, it could prevent neurodegeneration in other brain areas and caused by other diseases. We previously used memantine to prevent functional damage and to retain morphology of cerebellar neurons and Bergmann glia in an optogenetic mouse model of spinocerebellar ataxia type-1 (SCA1). However, before suggesting wider use of memantine in clinics, its side effects must be carefully evaluated. Blockers of NMDA receptors are controversial in terms of their effects on anxiety. Here, we investigated the effects of chronic application of memantine over 9 weeks to CD1 mice and examined rotarod performance and anxiety-related behaviors. Memantine-treated mice exhibited an inability to adapt to anxiety-causing conditions which strongly affected their rotarod performance. A tail suspension test revealed increased signs of behavioral despair. These data provide further insights into the potential deleterious effects of memantine which may result from the lack of adaptation to novel, stressful conditions. This effect of memantine may affect the results of tests used to assess motor performance and should be considered during clinical trials of memantine in patients.

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Galantamine for Alzheimer’s Disease and Alzheimer’s Disease with Cerebrovascular Disease

Davis

2016

Practical Pharmacology for Alzheimer’s Disease

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Acute Pharmacokinetics of Memantine in the Mouse

Cited by 9 publications

References 39 publications

Pharmacokinetic Properties of Memantine after a Single Intraperitoneal Administration and Multiple Oral Doses in Euploid Mice and in the Ts65Dn Mouse Model of Down's Syndrome

Pharmacokinetic Properties of Memantine after a Single Intraperitoneal Administration and Multiple Oral Doses in Euploid Mice and in the Ts65Dn Mouse Model of Down's Syndrome

Memantine Disrupts Motor Coordination through Anxiety-like Behavior in CD1 Mice

Galantamine for Alzheimer’s Disease and Alzheimer’s Disease with Cerebrovascular Disease

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