GABA & Glutamate.1per

GABA & Glutamate.1per - PHARMACOLOGY OF GABA &...

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PHARMACOLOGY OF GABA & GLUTAMATE SYSTEMS Chap. 11 Golan Fri. Jan. 21 1
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OBJECTIVES Understand the physiology of GABAergic and glutamatergic neurotransmission. Understand how pharmacologic agents can modify GABA Learn the mechanisms of action & the properties of the main classes of drugs active at GABAergic sites and the prototype agents. Understand how pharmacologic agents affecting glutamate activity may be useful in treating some neurologic disorders. 2
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Excitatory & Inhibitory Transmitters 3
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The GABAergic Synapse GAT-1 Glutamate GABA GABA GABA http://hubnet.buffalo.edu:2168/resourceTOC.aspx?resourceID=28 GABA Ca 2+ GAT-1 4
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The GABAergic Synapse http://hubnet.buffalo.edu:2168/resourceTOC.aspx?resourceID=28 Vigabatrin X GABA Glutamate Valproate X + GABA Glial Uptake GABA Tiagabine X X X GAT-1 Glutamate GABA GABA GABA GABA GABA GABA GABA GABA GABA GABA 5
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Synthetic Pathways between 6
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The GABA A Receptor 7
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The GABA A Receptor 8
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The GABA B Receptor 9
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P ARTIAL L IST OF GABA- ERGIC A GENTS Drug Class Mechanism Effects GABA synthesis: Allylglycine Isoniazid Inhibits GAD Inhibits pyridoxal kinase Convulsant GABA release: Tetanus toxin Inhibits GABA & glycine release Convulsant GABA turnover : Tiagabine Vigabatrine Inhibits GAT-1 Inhibits GABA transaminase Anti-convulsant GABA-A Rec agonist: Muscimol Gaboxadol Receptor A agonists Mimics psychosis Anticonvulsant GABA-A Rec antagonist: Bicuculine, Gabazine Picrotoxin Receptor A antagonists Convulsants GABA -A modulators: Benzodiazepines Barbiturates Potentiate GABA binding GABA efficacy (& weak agonist for barbs) Anticonvulsant, anxiolytic Anticonvulsant, anesthetic GABA-B Rec agonist: Baclofen Receptor B agonist Muscle relaxant 10
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Effects of Modulators on Potency & EfFcacy of GABA-A Receptors Fig. 11-6 11
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GABA & Glutamate.1per - PHARMACOLOGY OF GABA &...

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