Glutamate

Glutamate, also known as glutamic acid, is the most abundant neurotransmitter in the vertebrate nervous system, and is involved in learning and memory. Glutamate is also used as a precursor in the body for forming GABA, the main inhibitory neurotransmitter.

Chemistry

Glutamate generally exists as a negatively-charged carboxylate, at pH values above 4.

The Glutamate System

There are two categories of glutamate receptors, named for the mechanism that gives rise to the postsynaptic current; ionotropic and metabotropic. Ionotropic receptors work via the movement of ions in and out on ligand-gated ion channels. Metabotropic receptors work via their activation of secondary messenger chemicals. These chemicals eventually induce the postsynaptic current, either through their own action or by activating the ligand-gated ion channels.

Drugs targeting the glutamate system

• Agonists

A glutamate agonist is a chemical that binds to and activates a glutamate receptor, and triggers a response, displaying full efficacy at that receptor.

• Positive Allosteric Modulators

A positive allosteric modulator is a substance which indirectly influences the effects of an agonist at a receptor, by binding to a site distinct from that of the agonist binding site. Usually they induce a structural change within the receptor structure. Many nootropics and ampakine (a class of compounds known to enhance attention span and alertness) drugs are positive modulators of the AMPA glutamate receptor. These include piracetam, aniracetam and unifiram.

• Antagonists

A glutamate receptor antagonist is a type of receptor drug that inhibits action at glutamate receptors. Ethanol acts as an antagonist against the NMDA, AMPA and Kainate glutamate receptors, along with several antiepileptic drugs. Many dissociative drugs are antagonists against the NMDA glutamate receptor, including ketamine, MXE, PCP and DXM. Tramadol and ibogaine are dual antagonists against the NMDA glutamate receptor and opioid receptors.

• Negative Allosteric Modulators

A negative allosteric modulator is a substance which indirectly influences the effects of an inverse agonist at a receptor, by binding to a site distinct from that of the inverse agonist binding site. Usually they induce a structural change within the receptor structure. Antiepileptic drugs are also found in this class.

See Also

• Acetylcholine
• Dopamine
• Serotonin
• Adrenaline
• Noradrenaline
• GABA
• Neurotransmitter