Barbital (Veronal)

• Barbital (Veronal) was used as a sedative-hypnotic for insomnia and anxiety management.
• It is a barbiturate that depresses CNS activity, producing sedation and sleep.

Chemical Formula:

• C₈H₁₂N₂O₃

Mechanism of Action:

• Enhances the action of GABA by prolonging the opening of Cl⁻ channels at the GABA-A receptor.

Therapeutic Uses:

• Historically used as a sedative/hypnotic (no longer in clinical use due to safety concerns).

Side Effects of Barbital:

• Drowsiness
• Respiratory depression
• Physical dependence
• Withdrawal symptoms

Structure-Activity Relationship (SAR):

1. Barbituric acid core (pyrimidine-2,4,6-trione):

   • Required for sedative-hypnotic activity.

2. Alkyl substitutions at position 5 (usually 2 groups):

   • Increase lipid solubility and CNS activity.
   • Optimal total carbon atoms = 6–10 for maximal hypnotic effect.

3. No substitution on the nitrogen:

   • Barbital has unsubstituted N1 and N3; gives moderate onset and long duration.

4. Highly polar:

   • Less lipophilic than others like phenobarbital; hence slower CNS penetration.

Synthesis of Barbital:

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