Doxylamine

Doxylamine is a sedating antihistamine used to treat insomnia and allergic symptoms. In combination with pyridoxine (vitamin B6), it is also used to treat morning sickness in pregnant women. It is also used in nighttime cold medications and in pain medications containing acetaminophen and codeine to aid sleep. The drug is available over the counter and is taken perorally.

Doxylamine is a first-generation antihistamine and was first synthesized in 1948 by Nathan Sperber and colleagues in the United States.

Pharmacodynamics

Doxylamine acts primarily as an antagonist of the histamine H1 receptor. This action is responsible for its antihistamine and sedative properties. To a lesser extent, doxylamine acts as an antagonist of muscarinic acetylcholine receptors, an action responsible for its anticholinergic and (at high doses) deliriant effects.

Pharmacokinetics

Doxylamine is very rapidly absorbed enterally. It is metabolized by the liver through the enzymes CYP2D6, CYP1A2, and CYP2C9 and excreted in the urine. The half-life is about 10 hours.

Side effects

• Dizziness
• drowsiness
• tiredness
• Dry mouth
• blurred vision
• Constipation
• Muscle incoordination
• Urinary retention
• mental confusion
• Delirium

In rare cases, potentially life-threatening intestinal obstruction may occur.

Toxicological data

Signs of overdose include wheezing, chest tightness, fever, pruritus, severe cough, blue skin color, seizures, swelling of face, lips, tongue, or throat.

LD50, mouse, oral: 470 mg-kg-1