Methohexital Sodium: Chemical Structure, Mechanism of Action, Structural Activity Relationship, Synthesis, Uses & Side Effects

Chemical Structure:

• C14H18N2O3Na

Chemical Structure

Mechanism of Action:

• GABA Receptor Agonist: Methohexital enhances the effect of gamma-aminobutyric acid (GABA) at the GABA_A receptor. This increases the flow of chloride ions into the neuron, leading to hyperpolarization and inhibition of neuronal firing.

• Rapid Onset: It is an ultra-short-acting barbiturate, inducing anesthesia by depressing the central nervous system, particularly the cerebral cortex and the reticular activating system.

Structural Activity Relationship (SAR) of Methohexital Sodium

1.Barbiturate Core:

• The barbiturate core structure is crucial for CNS depressant activity. Alterations to this ring significantly affect potency and duration of action.

2.Substitutions at C5:

• Methohexital has an ethyl group at C5. This substitution modulates its anesthetic properties, where variations can affect lipid solubility, onset, and duration of action.

3.Oxygen Substitution at C2:

• The oxygen atom at C2 is essential for barbiturate activity. This feature influences binding to the receptor site.

4.Alkylation at N1:

• Methohexital has a methylhexyl side chain at N1. The length and branching of this alkyl side chain are crucial for hypnotic potency, with longer chains generally increasing lipid solubility and potency.

5.Sodium Salt Form:

• The sodium salt form enhances water solubility, facilitating intravenous administration.

SAR of Methohexital Sodium

Synthesis of Methohexital Sodium

The synthesis of Methohexital sodium from barbituric acid involves several steps:

1.Alkylation of Barbituric Acid:

• Barbituric acid + Ethyl bromide → 5-Ethylbarbituric acid

2.Introduction of the N1 Side Chain:

• 5-Ethylbarbituric acid + 1-Bromo-3-methylbutane → Methohexital

3.Formation of Sodium Salt:

• Methohexital + NaOH → Methohexital sodium

Uses:

• Induction of Anesthesia: Often used for the rapid induction of anesthesia.

• Sedation for Short Procedures: Suitable for sedation in short diagnostic and therapeutic procedures.

Side Effects:

• Respiratory Depression: Can cause apnea and hypoventilation.

• Cardiovascular Effects: Hypotension and tachycardia may occur.

• Nervous System: Potential for excitatory phenomena, such as muscle twitching or even seizures, especially in pediatric patients.

• Allergic Reactions: Rare, but possible, including anaphylaxis.

• Pain on Injection: Common when administered peripherally.