Methadone Hydrochloride

• Methadone Hydrochloride manages opioid dependence and chronic pain with long-lasting effects.
• It acts as a μ-opioid receptor agonist with NMDA antagonism for analgesia.

Chemical Formula:

• C₂₁H₂₇NO·HCl

Mechanism of Action:

• Full μ-opioid receptor agonist
• Also, NMDA antagonist and inhibits monoamine reuptake
• Very long half-life (15–60 hrs) → minimal withdrawal fluctuations

Uses of Methadone Hydrochloride:

• Opioid maintenance therapy (OMT) in addiction treatment
• Chronic severe pain

Side Effects of Methadone Hydrochloride:

• Respiratory depression (long-lasting)
• QT prolongation
• Sedation
• Constipation

SAR of Methadone:

1. Diphenylpropylamine structure:

   • Central for opioid activity.

2. Tertiary amine:

   • Protonated form interacts with μ-opioid receptors.

3. Two phenyl rings:

   • Important for receptor binding; contribute to potency.

4. Ketone group:

   • Increases polarity and contributes to partial NMDA antagonism.

5. Chiral center:

   • (R)-methadone is the active isomer at opioid receptors.

6. Extended duration of action:

   • Due to slow metabolism and high lipophilicity.

Synthesis of Methadone:

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