Glutamate is the major excitatory neurotransmitter in the brain and is involved in cognitive functions like learning and memory. It has two major classes of receptors - ionotropic and metabotropic receptors. Glutamate is synthesized from glutamine via the glutamate-glutamine cycle and stored in vesicles for release. It is transported back into glial cells via glutamate transporters and converted back to glutamine. Drugs can target ionotropic receptors as antagonists to treat conditions caused by glutamate toxicity like neurodegeneration, ischemia and seizures.

1. ADVANCED PHARMACOLOGY
TOPIC : GLUTAMATE
AYANA R KUMAR
M Pharm
Department of Pharmacology

2. GLUTAMATE
 Glutamate is a Excitatory neurotransmitter.
 Glutamate generally refers to the anion of glutamic
acid.
 Glutamate is involved in cognitive functions such
as learning and memory in the brain.
 Biochemical receptors for glutamate fall into two
major classes,
1. IONOTROPIC RECEPTORS
2. METABOTROPIC RECEPTORS

3. BIOSYNTHESIS
 Synthesized from Glutamine.
 Glutamate-Glutamine cycle.

4. STORAGE
 Stored in vesicles in the axon.
 Released by an increased concentration of
intracellular Ca2+.
 Synaptic release of glutamate is controlled by a
wide range of presynaptic receptor.

5. GLUTAMATE TRANSPORTERS
 Glutamate uptake
 Na+/H+/K+ dependent transporters.
 Glutamate taken up by astroglial cells is converted
to Glutamine.
Glutamate-Glutamine
Nerve terminals take up Glutamine and
convert Glutamine back to glutamate.

6. GLUTAMATE RECEPTORS
 Receptors are responsible for the glutamate-
mediated postsynaptic excitation of neural cells.
 Glutamate receptors can be divided into two
groups,
1. IONOTROPIC RECEPTORS
2. METABOTROPIC RECEPTORS

8. IONOTROPIC RECEPTORS
 Ligand-gated ion channels.
 Allow the flow of K+, Na+ and sometime Ca2+.

9. METABOTROPIC RECEPTORS
 G protein–linked receptors
 fly- trap like structure

10. MECHANISM OF ACTION

12. DRUGS ACTING ON
GLUTAMATE RECEPTORS
GLUTAMATE RECEPTOR
ANTAGONIST
 Glycine site blocking drug : Kynureneic acid
 Channel blocking drugs:Ketamine,
Phencyclidine,Dizocilpine,Remacimide,Memantin
e
 NMDA receptor antagonist : Selfotel,
Eliprodil,Dextromethorphan,Methadone,
Amantadine.

13.  GLUTAMATE RECEPTOR AGONIST
 AMPA Receptor modulators:Cyclothiazide, Piracetam and
CX-516 (Ampalex).
Role : Cognition enhancement
Treatment of schizophrenia, Depression, Attention deficit
hyperactivity disorder (ADHD) and Parkinson's disease.

14. THANK YOU

15. GLUTAMATE TOXICITY
 Excitotoxicity
 Neurodegeneration
 Aching
 Autism
 Ischemia
 Seizures