Promethazine hydrochloride

Structure (Promethazine hydrochloride)

• Promethazine hydrochloride possesses a tricyclic structure with two benzene rings fused to a central carbon and connected to a dimethylaminoethyl side chain.

• The hydrochloride salt enhances solubility.

• Chemical Formula: C₁₇H₂₈N₂S·HCl

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  Structure Promethazine hydrochloride

Mode of Action

• Acts as a potent H₁-receptor antagonist with strong anticholinergic and sedative effects.

• It also exhibits antiemetic and analgesic properties.

Uses

• Allergic Reactions: Effective in treating symptoms like itching, sneezing, and runny nose.

• Nausea and Vomiting: Used as an antiemetic for motion sickness and post-operative nausea.

• Sedation: Utilized as a sedative and sleep aid.

• Cold Symptoms: Helps alleviate nasal congestion and other related discomforts.

Structure-Activity Relationship (SAR)

1. Phenothiazine Core: Essential for H₁ antagonism and contributes to the drug's lipophilicity, enhancing blood-brain barrier penetration.

2. Dimethylamino Group: Critical for binding to H₁ receptors through hydrogen bonding.

3. Tricyclic Structure: Provides rigidity and the necessary spatial orientation for effective receptor interaction.

4. Substituents: Modifications on the benzene rings can alter potency and selectivity.

5. Sulfoxide Group: Contributes to metabolic stability and activity.

Synthesis

• Promethazine can be synthesized through the reaction of chlorodiphenylmethane with piperazine, followed by methylation.

Synthetic Route:

• Promethazine can be synthesized via the following pathway:

• Formation of Phenothiazine: React 2-amino-10-methylphenothiazine with an appropriate electrophile.

• Alkylation: The dimethylamino side chain is introduced through alkylation with dimethyl chloride.

• Salt Formation: The free base is converted to its hydrochloride salt by reaction with hydrochloric acid to enhance solubility.