Structure–Activity Relationship (SAR) of Anticonvulsants

• Structure–Activity Relationship (SAR) of Anticonvulsants explains molecular features crucial for seizure control.
• Structure–Activity Relationship (SAR) of Anticonvulsants links chemical modifications to efficacy and safety.
• Anticonvulsants vary structurally but share key SAR features within their classes:

1. Hydantoins (e.g., Phenytoin):

   • Diphenyl groups on the hydantoin ring are crucial.
   • Electron-withdrawing groups enhance potency.
   • Hydrogen bonding supports sodium channel binding.

2. Barbiturates (e.g., Phenobarbital):

   • C-5 substitutions affect lipid solubility and CNS activity.
   • Alkyl/aryl groups enhance brain penetration.
   • Ureide core is vital for GABA-A receptor interaction.

3. Succinimides (e.g., Ethosuximide):

   • Alpha-methyl substitution improves selectivity for T-type calcium channels.
   • Mainly used for absence seizures.

4. Iminostilbenes (e.g., Carbamazepine):

   • Tricyclic core is essential.
   • Active metabolite: carbamazepine epoxide.
   • Aromatic substitutions affect efficacy and toxicity.

5. Newer Agents:

   • Gabapentin: GABA analog; binds to α2δ subunit of calcium channels, not GABA receptors.
   • Lamotrigine: Blocks sodium channels; requires aromatic rings and N-heterocycles.

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