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Use of glutamate antagonists for the treatment of cancer

a glutamate antagonist and cancer technology, applied in the field of glutamate antagonists for cancer treatment, can solve the problems of reducing the binding capacity of glutamate receptors, no link has been established so far between glutamate receptor stimulation and tumor growth, and achieves significant concentration-dependent antiproliferation effect and enhanced tumoricidal effect of cytostatic agents

Inactive Publication Date: 2005-03-10
IKONOMIDOU HRISSANTHI
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  • Abstract
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Benefits of technology

In addition, NMDA and AMPA antagonists enhanced tumoricidal effect of cytostatic agents (FIG. 3-5). Each of the cytostatic agents tested produced a significant tumoricidal effect on its own at the concentrations used, which reached a peak for all three agents after 72 hrs exposure time. The NMDA antagonist MK 801 and the AMPA antagonists GYKI 52466 and NBQX significantly (P<0.05-0.001) potentiated tumoricidal effect of cisplatin, vinblastin and thiotepa when used in combination with the cytostatic agents. This potentiation of the tumoricidal effect of the cytostatic agents by the NMDA and the AMPA antagonists was most pominent after an exposure time of 72 hrs for cisplatin and thiotepa and 48 hrs for vinblastin (FIGS. 3-5).

Problems solved by technology

However, no link has been established so far between glutamate receptor stimulation and tumor growth.
These soluble forms can be used to circulate and to bind to glutamate and therefore decrease its binding capability to the receptors.

Method used

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  • Use of glutamate antagonists for the treatment of cancer
  • Use of glutamate antagonists for the treatment of cancer
  • Use of glutamate antagonists for the treatment of cancer

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Embodiment Construction

The tumor cell lines used in the context of this invention have been obtained from human tumors. Agents active against tumor growth in vitro have proved to also be effective anticancer agents in vivo.

The surprising observation that glutamate antagonists have antiproliferative actions in tumor cells and that the tumoricidal effect of three different cytostatic agents, cisplatin, vinblastin and thiotepa is significantly enhanced by two different AMPA antagonists, GYKI 52466 and NBQX (2,3-dihydroxy-6-nitro-7-sulfaoylbenzo-(F)-quinoxaline) and the NMDA antagonist MK 801 is described in the following paragraphs.

Cell lines and culture. Human neuroblastoma (SKNAS), human rhabdomyosarcoma / medulloblastoma (TE671), human brain astrocytoma (MOGGCCM), human thyroid carcinoma (FTC238), human Caucasian lung carcinoma (A549), human Caucasian colon adenocarcinoma (LS180) and human breast carcinoma (T47D) were obtained from European Collection of Cell Cultures (ECACC), Center for Applied Microb...

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Abstract

Disclosed are methods for treating cancer by administering an inhibitor of the interaction of glutamate with the NMDA / glycine / polyamine receptor / ion channel complex.

Description

TECHNICAL FIELD Pharmaceutical compositions and their uses BACKGROUND ART Glutamate is a major neurotransmitter but possesses also a wide metabolic function in the body. It is released from approximately 40% of synaptic terminals and mediates many physiological functions by activation of different receptor types (Watkins and Evans (1981) Excitatory amino acid transmitters, Annu. Rev. Pharmacol., 21: 165-189; Gasic and Hollmann (1992) Molecular neurobiology of glutamate receptors, Annu. Rev. Physiol., 54: 507-536). Two main categories of glutamate receptors have been identified, ionotropic and metabotropic (Bettler and Mulle, (1995) Neurotransmitter Receptors II, AMPA and Kainate Receptors, Neuropharmacology, 34: 123-139; Pin and Duvoisin (1995) Neurotransmitter receptors I, The Metabotropic Glutamate Receptors: Structure and Functions, Neuropharmacology, 34: 1-26; Mori and Mishina (1995) Neurotransmitter Receptors VIII, Structure and Function of the NMDA Receptor Channel, Neuropha...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K31/4355A61K31/439A61K31/498A61K31/5513A61K45/06A61P35/00A61P43/00
CPCA61K31/439A61K45/06A61K31/5513A61K31/498A61P35/00A61P43/00
Inventor IKONOMIDOU, HRISSANTHI
Owner IKONOMIDOU HRISSANTHI
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