Glutamatergic mechanisms in different disease states: overview and therapeutical implications - An introduction
by
Tzschentke TM.
Grunenthal GmbH,
Research and Development,
Aachen, Germany.
Amino Acids 2002;23(1-3):147-52 40

ABSTRACT

Glutamate is the most widely distributed excitatory transmitter in the central nervous system (CNS). It is acting via large - and still growing - families of receptors: NMDA-, AMPA-, kainate-, and metabotropic receptors. Glutamate has been implicated in a large number of CNS disorders, and it is hoped that novel glutamate receptor ligands offer new therapeutic possibilites in disease states such as chronic pain, stroke, epilepsy, depression, drug addiction and dependence or Parkinson's disease. While an extensive preclinical literature exists showing potential beneficial effects of NMDA-, AMPA-, kainate- and metabotropic receptor ligands, only NMDA receptor antagonists have been characterized clinically to any appreciable degree. In these trials it has been shown that while several compounds are therapeutically active, they also produce serious side effects at therapeutic doses. Current interest largely centers on the development of receptor subtype-selective compounds, namely compounds selective for receptors containing the NR2B subunit. Preclinical findings and the first clinical results are encouraging, and it may be that such subunit-selective compounds may have a sufficiently wide therapeutic window to be safe for human use.

NMDA
Serotonin
Dopamine
Memantine
Monoamines
21st Century
Noradrenaline
Neurotrophins
NMDA antagonists
New antidepressants
Glutamate and GABA
Dextromethorphan (DM)
Glutamate and depression
Glutamate and mood disorders
Depression and antidepressants
Glutamate-modulating drugs for mood disorders

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