Carbamazepine

• Carbamazepine treats epilepsy, trigeminal neuralgia, and bipolar disorder effectively
• It stabilizes neuronal membranes by blocking voltage-gated sodium channels.

Formula:

• C₁₅H₁₂N₂O

Mechanism of Carbamazepine:

• Na⁺ channel blocker → inhibits repetitive neuronal firing
• Also modulates glutamate release

Uses of Carbamazepine:

• Focal & generalized tonic-clonic seizures
• Trigeminal neuralgia
• Bipolar disorder (mania)

Side Effects:

• Diplopia, ataxia
• SIADH → hyponatremia
• Aplastic anemia, agranulocytosis
• SJS/TEN (esp. HLA-B*1502 in Asians)
• CYP450 autoinduction

SAR of Carbamazepine:

1. Dibenzazepine ring system:

   • Tricyclic structure is crucial for activity.

2. Double bond in azepine ring:

   • Maintains rigid conformation important for binding.

3. Carboxamide group at position 5:

   • Key functional group for anticonvulsant action.

4. Aromatic rings:

   • Contribute to lipophilicity and CNS activity.

5. Stereochemistry:

   • Rigid tricyclic structure enhances selectivity for sodium channels.

6. Metabolism to epoxide (active metabolite):

   • Contributes to overall pharmacologic effect.

Synthesis of Carbamazepine:

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