Question 9

Describe the physiological basis for the mechanism of action of three commonly used anticonvulsant groups. Give an example of a drug for each mechanism of action.

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College Answer

The three main anticonvulsant mechanisms required were:

1. Sodium channel blockers. These promote the inactive state of voltage activated Na
channels. Sodium channels are unable to open for a period of time making the neuron
more refractory to action potential generation. Rapid repetitive firing is diminished and
spread of electrical activity to adjacent brain areas is suppressed.
Examples: phenytoin, carbamazepine, lamotrgine, Na valproate

2. Drugs that enhance GABA mediated synaptic inhibition. This increases the influx of
chloride ions into the cell and hyperpolarizes the neuron. 3 mechanisms:
a. Act on GABA receptor. Example: benzodiazepines, barbiturates

b. Inhibit GABA transporter and reduce neuronal GABA reuptake. Example: tiagabine.
c. Promote GABA release. Example: gabapentin.

3. Drugs that inhibit Calcium channels. Limit activation of voltage activated Ca channel
known as the T current. Example.: Na valproate
Other mechanisms of action with examples if described earned extra marks. These included
glutamate /NMDA receptor inhibition. Example: magnesium.


It is impossible to guess how much detail they wanted for "extra marks", but hopefully something like this would be enough:

Mechanism/class Drug target Examples

Ion channel modulators:

reduce neuronal excitability by altering the resting membrane potential,  stabilising the channels involved in the conduction of action potentials, or inhibiting the intracellular calcium flux which triggers  excitatory neurotransmitter release.

 K+ channels
  • Retigabine (ezogabine)
Ca2+ channels
  • Ethosuximide
  • Gabapentin
  • Pregabalin
  • Paramethadione 
  • Zonisamide
Na+ channels
  • Phenytoin
  • Carbamazepine
  • Lacosamide
  • Lamotrigine
  • Rufinamide
  • Sodium valproate
  • Topiramate
GABA potentiators: Increased inhibitory neurotransmission by either directly affecting the GABA ligand-gated chloride channel, decreasing the reuptake of GABA from the synapse, or decreasing the breakdown of GABA. GABAA
  • Benzodiazepines
  • Barbiturates
  • Clobazam
  • Primidone
GABA reuptake transporter
  • Tiagabine
GABA catabolism
  • Vigabatrin
  • Sodium valproate
Presynaptic neurotransmitter release modulators: decrease the release of neurotransmitters SV2A
  • Levetiracetam
Postsynaptic inhibitors of neurotransmission: decrease the effect of released neurotransmitter ligands on their receptors AMPA 
  • Perampanel
  • Topiramate
  • Ketamine
  • Sodium valproate
  • Magnesium
God only knows what effect  
  • Paraldehyde
  • Potassium bromide


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Perucca, Emilio. "Pharmacological and therapeutic properties of valproate." CNS drugs 16.10 (2002): 695-714.

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Albani, F., R. Riva, and A. Baruzzi. "Carbamazepine clinical pharmacology: a review." Pharmacopsychiatry 28.06 (1995): 235-244.

Tomson, Torbjörn. "Clinical pharmacokinetics of carbamazepine." Cephalalgia 7.4 (1987): 219-223.

Kuo, Chung-Chin, et al. "Carbamazepine inhibition of neuronal Na+ currents: quantitative distinction from phenytoin and possible therapeutic implications." Molecular pharmacology 51.6 (1997): 1077-1083.