Strong H₁-histamine receptor antagonist; moderate muscarinic (anticholinergic) blockade; weak antagonism at 5-HT₂, D₂ and α-adrenergic receptors; non-competitive NMDA receptor antagonist

For Research Only

A. Chemical & Physical Properties

• A1. Identity & Structure

  • Empirical formula: C₁₇H₂₀N₂S·HCl

  • IUPAC name: (RS)-N,N-Dimethyl-1-(10H-phenothiazin-10-yl)propan-2-amine monohydrochloride

• A2. Molecular Weight & CAS

  • CAS No.: 58-33-3

  • M.W.: 320.88 g/mol

• A3. pKa

  • pKa (conjugate acid): 9.1

• A4. Appearance & Stability

  • White to faint-yellow crystalline powder; odorless; slow oxidation in air (blue discoloration)

• A5. Solubility & pH

  • Freely soluble in water (≥100 mg/mL at 25 °C) and soluble in alcohol

  • Typical oral solution pH: 4.7–5.2

B. Pharmacology & Uses

• B1. Mechanism of Action

  • Strong H₁-histamine receptor antagonist; moderate muscarinic (anticholinergic) blockade; weak antagonism at 5-HT₂, D₂ and α-adrenergic receptors; non-competitive NMDA receptor antagonist

• B2. Clinical Indications

  • Allergic reactions (hay fever, urticaria)

  • Nausea/vomiting (motion sickness, postoperative, chemotherapy)

  • Sedation/insomnia

  • Adjunct in common cold, hemolytic disease of the newborn

  • Anxiety before surgery

• B3. Routes & Dosage Forms

  • Oral tablets: 12.5–25 mg

  • Oral syrup: typically 6.25 mg/5 mL

  • Rectal suppositories: 12.5 mg

  • Injectable solution: 25 mg/mL

C. Pharmacokinetics

• C1. Absorption

  • ~88% absorbed; first-pass reduces absolute bioavailability to ~25%

• C2. Distribution

  • ~93% plasma protein bound

• C3. Metabolism & Elimination

  • Hepatic glucuronidation and sulfoxidation; t½ 10–19 h; excreted via urine and bile

D. Formulation Considerations

• D1. pH & Buffering

  • Maintain formulation pH 4.7–5.2 (e.g., citrate buffer) to ensure salt stability and solubility

• D2. Light & Oxidation

  • Protect from light/air; use amber glass or opaque containers to minimize blue oxidation

E. Safety & Side Effects

• E1. Common AEs

  • Sedation/drowsiness, dizziness, dry mouth, blurred vision, urinary retention

• E2. Warnings & Contraindications

  • Contraindicated in children < 2 years (respiratory depression), hypersensitivity, narrow-angle glaucoma, prostatic hypertrophy

  • Caution in elderly (anticholinergic burden), hepatic/renal impairment

F. Regulatory Status

• Prescription-only in the US; POM in the UK; OTC in Canada; S3 in Australia