Chlorpromazine Hydrochloride

• Chlorpromazine Hydrochloride blocks dopamine receptors, offering sedative and antipsychotic properties.
• Chlorpromazine Hydrochloride treats schizophrenia, nausea, and anxiety through its antipsychotic effects.

Chemical Formula:

• C₁₇H₁₉ClN₂S·HCl

Mechanism of Action:

• Strong D2 receptor blocker (limbic system, basal ganglia)
• Also blocks α1-adrenergic, muscarinic, and histamine H1 receptors

Therapeutic Uses:

• Schizophrenia
• Acute psychosis
• Severe agitation
• Intractable hiccups
• Nausea and vomiting

Side Effects:

• Sedation (H1 blockade)
• Hypotension (α1 blockade)
• Extrapyramidal symptoms (EPS)
• Tardive dyskinesia
• Neuroleptic malignant syndrome
• Photosensitivity
• Cholestatic jaundice

SAR of Chlorpromazine and Phenothiazines

1. Phenothiazine ring system:

   • Tricyclic core essential for antipsychotic activity.

2. Electron-withdrawing group at position 2 (e.g., Cl):

   • Enhances potency by increasing affinity for D₂ receptors.

3. 3-carbon linker chain:

   • Optimal distance between the nitrogen and tricyclic ring for D₂ receptor antagonism.

4. Terminal amine:

   • Tertiary amine is common; pKa influences CNS penetration.
   • Substituents can affect potency and side effect profile (sedation, EPS).

5. Lipophilicity:

   • Affects CNS penetration and onset.

Synthesis of Chlorpromazine

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