Halothane: Chemical Structure, Mechanism of Action, Structural-Activity Relationship, Synthesis, Uses & Side Effects

Chemical Structure:

• C2HBrClF3

Chemical Structure

Mechanism of Action:

• Central Nervous System: Primarily acts by depressing the central nervous system. It potentiates the effects of GABA (an inhibitory neurotransmitter), which leads to hyperpolarization and inhibition of neuronal firing.

• Lipid Membrane Interaction: Halothane integrates into the lipid bilayer of cell membranes, altering their physical properties and thus affecting ion channel function. This can disrupt the normal function of various ion channels, particularly those involved in nerve impulse propagation.

• Calcium Regulation: It may also interfere with the regulation of intracellular calcium, which is crucial in various cellular processes, including muscle contraction and neurotransmitter release.

Structural-Activity Relationship (SAR) of Halothane:

1.Halogen Substituents:

• The presence of bromine and chlorine atoms in halothane is crucial for its anesthetic potency.

• These halogens increase the lipophilicity (fat solubility) of the molecule, which is important for its action in the lipid-rich environment of the central nervous system.

2.Trifluoromethyl Group:

• The trifluoromethyl group contributes significantly to the anesthetic potency and the stability of the molecule.

• Fluorine atoms increase the hydrophobicity and the inertness of the molecule, making it less likely to undergo metabolism and reducing the risk of toxic metabolites.

3.Lack of Double Bonds or Aromatic Rings:

• Halothane does not contain double bonds or aromatic rings.

• The absence of these structures is advantageous in terms of reducing the potential for toxic metabolite formation during metabolism.

4.Molecular Size and Shape:

• The size and shape of halothane allow it to easily pass through the blood-brain barrier, a key feature for inhalational anesthetics.

SAR of Halothane

Synthesis of Halothane:

• here's a simplified chemical reaction for the synthesis of Halothane:

• CHCl3 + BrF3 → CBrClF2 + HF + ClF

• In this reaction:

• Chloroform (CHCl3CHCl3​) reacts with bromine trifluoride (BrF3BrF3​).

• The product is Halothane (CBrClF2CBrClF2​), along with hydrogen fluoride (HFHF) and chlorine fluoride (ClFClF) as byproducts.

Uses:

• Anesthesia: Used in general anesthesia, though its use has declined due to concerns about liver toxicity and other side effects.

• Pediatric Anesthesia: Previously popular in pediatric anesthesia due to its rapid onset and non-irritating properties.

Side Effects:

• Hepatotoxicity: A significant concern, particularly in repeated exposures or in adults, where a rare but severe form of liver damage (halothane hepatitis) can occur.

• Malignant Hyperthermia: A life-threatening condition caused by a genetic predisposition, leading to a hypermetabolic state.

• Cardiovascular Effects: Can cause arrhythmias and hypotension.

• Respiratory Effects: Like other general anesthetics, it can depress respiratory function.