Amino acids which cause excitatory pastsynaptic potential are called as excitatory amino acids (EAA) and such acidic amino acids as L-glutamate, L-aspartate, L-homocysteine acid and quinolinic acid are known as internal substances. It is presumed that neurons using the said amino acids as the transmitters play the central role in the excitatory neurons of the mammalian brain. As a result of the recent rapid progress of the active researches conducted on the mechanism of the EAA transmission the relationship between a wide range of functions of the brain and the disorders of the brain is being unraveled. It has been found that in medicaments causing the disorders very similar to schizophrenia is there is a medical substance which intercepts the actions of the EAA receptors of the type of NMDA(N-methyl-D-aspartate). Accordingly strong attentions have been drawn on a probable participation of the disorders of the EAA transmission in schizophrenia.
As mentioned above the L-glutamate or the L-aspartate, which are amino acids, is a neurotransmitter causing the primary excitotoxic action in the central nervous system. By a number of researches it has been unraveled that the above-mentioned excitatory amino acid relates to a wide range of neurophysiological functions including synaptic transmission, the regulation and the long-term potentiation of neurotransmitters, learning and memory, the flexibility of synaptic generation, ischemic hypoxic disorders and neuronal death, and the cause of several neurodegenerative disorders.
For example, in Alzheimer's or cerebrovascular dementia distinguishing primarily the deterioration of the brain actions the deterioration of glutamatergic transmission is considered to be the cause, and also, the disorder of the glutamatergic transmission is found in schizophrenia.
Glutamate receptors which exist locally in synaps have been classified into the followings according to the receptor's affinity with specific ligand and electrophysiological or neurochemistric actions.
The NMDA (N-methyl-D-aspartate) receptor related to an ion channel characterizing the penetrability of monovalent and divalent cations such as sodium ions and calcium ions and the blockade of magnesium ions.
The AMPA (.alpha.-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor related to an ion channel characterizing the penetrability of monovalent cations such as sodium.
The KA (kainate) receptor which is similar to the AMPA receptor in the ion characteristics but different from the AMPA receptor in both the conductance and the level of desensitization.
(The AMPA receptor and the KA receptor are sometime called collectively as the non-NMDA receptor.)
It is useful to develop potentiating substances of glutamatergic transmission to be used for the prophylactic and medical treatment of the neurodegenerative disorders in the said state of diseases.