|Trade names||Unisom, Vicks Formula 44 (in combination with Dextromethorphan), others|
|Metabolism||Hepatic (CYP2D6, CYP1A2, CYP2C9)|
|Elimination half-life||10–12 hours|
|Excretion||Urine (60%), feces (40%)|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||270.369 g·mol−1|
|3D model (JSmol)|
Doxylamine is a first-generation antihistamine used as a short-term sedative and hypnotic (sleep aid) or in combination formulations to provide night-time allergy and cold relief. It provides a calmative effect in preparations containing the analgesics paracetamol (acetaminophen) and codeine. It is prescribed in combination with vitamin B6 (pyridoxine) to prevent morning sickness in pregnant women. Its fetal safety rating is "A" (no evidence of risk).
It was first described in 1948.
Doxylamine is an antihistamine used to treat sneezing, runny nose, watery eyes, hives, skin rash, itching, and other cold or allergy symptoms. It is also used as a short-term treatment for sleep problems (insomnia).
It is used in the combination drug pyridoxine/doxylamine to treat nausea and vomiting of pregnancy.
As of 2004, doxylamine and diphenhydramine were the agents most commonly used to treat short-term insomnia. As of 2008, antihistamines were not recommended by the American Academy of Sleep Medicine for treatment of chronic insomnia "due to the relative lack of efficacy and safety data".
Doses of doxylamine that have been used for sleep range from 5 to 50 mg, with 25 mg being the typical dose.
Doxylamine succinate is a potent anticholinergic and has a side-effect profile common to such drugs, including dry mouth, ataxia, urinary retention, drowsiness, memory problems, inability to concentrate, hallucinations, psychosis, and a marked increased sensitivity to external stimuli.
Because of its relatively long elimination half-life (10–12 hours), doxylamine is associated with daytime/next-day drowsiness, grogginess, dry mouth, and tiredness when used as a hypnotic. The shorter elimination half-life of diphenhydramine (4–8 hours) may give it an advantage over doxylamine in this regard.
Unlike with diphenhydramine, case reports of coma and rhabdomyolysis have been reported with doxylamine.
Doxylamine succinate is generally safe for administration to healthy adults. The median lethal dose (LD50) is estimated to be ~500 mg/kg in humans. Symptoms of overdose may include dry mouth, dilated pupils, insomnia, night terrors, euphoria, hallucinations, seizures, rhabdomyolysis, and death. Fatalities have been reported from doxylamine overdose. These have been characterized by coma, tonic-clonic (or grand mal) seizures and cardiorespiratory arrest. Children appear to be at a high risk for cardiorespiratory arrest. A toxic dose for children of more than 1.8 mg/kg has been reported. A 3-year-old child died 18 hours after ingesting 1000 mg doxylamine succinate. Rarely, an overdose results in rhabdomyolysis and acute kidney injury.
Studies of doxylamine's carcinogenicity in mice and rats have produced positive results for both liver and thyroid cancer, especially in the mouse. The carcinogenicity of the drug in humans is not well studied, and the IARC lists the drug as "not classifiable as to its carcinogenicity to humans".
|Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.|
Doxylamine acts primarily as an antagonist or inverse agonist 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 the muscarinic acetylcholine receptors, an action responsible for its anticholinergic and (at high doses) deliriant effects.
The bioavailability of doxylamine is 24.7% for oral administration and 70.8% for intranasal administration. The Tmax of doxylamine is 1.5 to 2.5 hours. Its elimination half-life is 10 to 12 hours (range 7 to 13 hours). Doxylamine is metabolized in the liver primarily by the cytochrome P450 enzymes CYP2D6, CYP1A2, and CYP2C9. The main metabolites are N-desmethyldoxylamine, N,N-didesmethyldoxylamine, and doxylamine N-oxide. Doxylamine is eliminated 60% in the urine and 40% in feces.
Doxylamine is a first-generation antihistamine sleep aid with weak hypnotic and calming effects first reported in 1949.[third-party source needed]
Doxylamine is primarily used as the succinic acid salt, doxylamine succinate.