Halothane

• Halothane enhances GABA activity, causing CNS depression and smooth muscle relaxation.
• It is an inhalation anesthetic used for induction and maintenance of general anesthesia.

Chemical Formula:

• C₂HBrClF₃

Mechanism of Action:

• Potentiates GABA-A and glycine receptor activity
• Inhibits NMDA receptors and neuronal excitability
• Alters membrane fluidity via interaction with lipid bilayer

Uses:

• Induction and maintenance of anesthesia
• Historically used in pediatric anesthesia

Side Effects:

• Halothane hepatitis (rare but severe hepatic necrosis)
• Cardiac arrhythmias due to sensitization to catecholamines
• Hypotension (vasodilation)
• Bradycardia
• Malignant hyperthermia (when used with succinylcholine)

SAR of Halothane:

1. Halogenated ethane structure:

   • Contains three fluorine atoms and one bromine and chlorine.
   • The halogens influence potency, lipid solubility, and stability.

2. Lipophilicity:

   • Increased fluorination improves CNS penetration and anesthetic potency.

3. Br atom:

   • Contributes to molecular weight and affects cardiac sensitization.

4. Asymmetry:

   • Causes chirality; racemic mixture used.

5. Metabolic liability:

   • Can undergo oxidative metabolism → formation of trifluoroacetyl halide → hepatotoxicity risk.

Synthesis of Halothane:

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