Glutamate

Excitatory neurotransmitter

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. G lutamate 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 S ynthesized from Glutamine. Glutamate-Glutamine cycle.

4. STORAGE Stored in vesicles in the axon. Released by an increased concentration of intracellular Ca 2+ . 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 G lutamine. Glutamate-Glutamine Nerve terminals take up Glutamine and convert Glutamine back to glutamate .

6. GLUTAMATE RECEPTORS R eceptors 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

7. IONOTROPIC RECEPTORS Ligand-gated ion channels. A llow the flow of K+, Na+ and sometime Ca2+.

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

9. MECHANISM OF ACTION

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

11. 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.

12. THANK YOU

13. GLUTAMATE TOXICITY Excitotoxicity Neurodegeneration Aching Autism Ischemia Seizures