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1 Mechanism of action of Antiepileptic Drugs Gitanjali-1: B. Gitanjali.

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Presentation on theme: "1 Mechanism of action of Antiepileptic Drugs Gitanjali-1: B. Gitanjali."— Presentation transcript:

1 1 Mechanism of action of Antiepileptic Drugs Gitanjali-1: B. Gitanjali

2 2 Cellular Mechanisms of Seizure Generation  Excitation (too much) Ionic-inward Na +, Ca ++ currents Neurotransmitter: glutamate, aspartate  Inhibition (too little) Ionic-inward Cl; outward K + currents Neurotransmitter: GABA Gitanjali-5:

3 3 AEDs: Molecular and Cellular Mechanisms  Phenytoin, Carbamazepine Block voltage-dependent sodium channels at high firing frequencies Gitanjali-6:

4 4 Na + Open Gitanjali-7: Inactivation gate Activation gate

5 5 Na + Carbamazepine Phenytoin Felbamate Lamotrigine Na+ Inactivated channel Block channels firing at high frequencies Barbiturates Topiramate Gitanjali-8:

6 6 AEDs: Molecular and Cellular Mechanisms  Barbiturates Prolong GABA-mediated chloride channel openings Some blockade of voltage- dependent sodium channels Gitanjali-9:

7 7 AEDs: Molecular and Cellular Mechanisms  Benzodiazepines Increase frequency of GABA- mediated chloride channel openings Gitanjali-10:

8 8 AEDs: Molecular and Cellular Mechanisms Valproate  May enhance GABA transmission in specific circuits  Blocks voltage-dependent sodium channels  Blocks T-type calcium currents Gitanjali-11:

9 9 GABA metabolites Succinic Semialdehyde Gabapentin GT: GABA transaminaseSSD:Succinic semialdehyde dehydrogenase GT SSD Vigabatrin Valproate Benzodiazepines Barbiturates Cl - Gabapentin Tiagabine Topiramate Gitanjali-12:

10 10 AEDs: Molecular and Cellular Mechanisms  Ethosuximide Blocks slow, threshold, “transient” (T-type) calcium channels in thalamic neurons Gitanjali-13:

11 11 Ca ++ Voltage regulated Ca ++ current, low threshold “T” current in thalamus Gitanjali-14: Involved in 3 per second spike and wave rhythm

12 12 Ca ++ Ethosuximide Valproate Reduction in the flow of Ca ++ through T - type Ca ++ channels in thalamus Gitanjali-15: Ca ++

13 13 Newer AEDs: Molecular and cellular Mechanisms Vigabatrin Irreversibly inhibits GABA- transaminase Tiagabine Interferes with GABA re-uptake Gitanjali-16:

14 14 Newer AEDs: Molecular and cellular Mechanisms Topiramate  Blocks voltage-dependent sodium channels at high firing frequencies ? Increases frequency at which GABA opens Cl - channels (different site from benzodiazepines) ? Antagonizes glutamate actions at receptor subtype Gitanjali-17:

15 15 Newer AEDs: Molecular and Cellular Mechanisms Felbamate May block voltage-dependent sodium channel at high firing frequencies May modulate NMDA receptor via strychnine insensitive glycine receptor Gitanjali-18:

16 16 AEDs: Molecular and Cellular Mechanisms Gabapentin May modulate amino acid transport into brain May interfere with GABA re-uptake Gitanjali-19:

17 17 Newer AEDs: Molecular and Cellular Mechanisms Lamotrigine Blocks voltage-dependent sodium channels at high firing frequencies May interfere with pathologic glutamate release Gitanjali-20:


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