gms | German Medical Science

55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

Continuous administration of the glutamate receptor antagonist memantine fails to supress orthotopic glioma growth

Kontinuierliche Gabe des Glutamatrezeptor-Antagonisten Memantine unterdrückt nicht das orthotope Gliomwachstum

Meeting Abstract

  • corresponding author Sandra Christiane Kunze - Neurochirurgische Klinik, Medizinische Fakultät der Universität Heidelberg, Mannheim
  • W. Danysz - Merz Pharmaceuticals, Frankfurt/Main
  • J. Woitzik - Neurochirurgische Klinik, Medizinische Fakultät der Universität Heidelberg, Mannheim
  • R. Erber - Neurochirurgische Klinik, Medizinische Fakultät der Universität Heidelberg, Mannheim
  • P. Vajkoczy - Neurochirurgische Klinik, Medizinische Fakultät der Universität Heidelberg, Mannheim

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocP 05.50

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/dgnc2004/04dgnc0333.shtml

Veröffentlicht: 23. April 2004

© 2004 Kunze et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Objective

Glutamate excitoxicity is involved in numerous CNS disorders. In addition, it has been suggested that glutamate is involved in the pathogenesis of malignant glioma and that inhibition of glutamate-mediated signalling may suppress tumor growth. The aim of the present study was to assess the effects of a continuous administration of the glutamate receptor antagonist memantine on orthotopic glioma growth.

Methods

500000 C6 rat glioma cells were implantated stereotactically (depth of 6mm, right striatum) into 16 male Wistar rats (200-250g). Before implantation, glutamate release/uptake of our C6 cell line was analyzed in vitro using a photometric, enzyme-kinetic analyzer. Following tumor implantation, rats were randomly assigned to two groups and received subcutaneous osmotic mini pumps loaded with memantine (n=8) or saline (n=8). Memantine loading dose was calculated to achieve continuous therapeutic levels over 14 days. Memantine plasma levels were controlled on days 2 and 14. After 14 days the rats were sacrified and their brains processed for histological analysis. Brain specimens were embedded in paraffin, serially sectioned (5mm), and tumor volume was determined using an image analysis system.

Results

Our C6 cells were characterized by a balanced glutamate release/uptake. Determination of memantine levels demonstrated that continuous administration of the drug had resulted in plasma levels well within the therapeutic range (day2, 144±12ng/ml; day14, 148±41ng/ml). Nevertheless, memantine failed to significantly supress tumor growth. Control tumors ranged between 4.6mm3 and 17.3mm3 (mean±SD:9.4±5.5mm3) and memantine treated tumors ranged between 3.5mm3 and 14.4mm3 (mean±SD:8.0±3.9mm3).

Conclusions

The glutamate receptor antagonist memantine is ineffective in suppressing orthotopic glioma growth, even if the compound is administered continuously at therapeutic levels that have been shown to be effective in preventing neuronal damage in other CNS disorders.