Hydroxyzine vs Diphenhydramine: what is the difference?

How they differ

Both are first generation antihistamines that cross into the brain and cause drowsiness, and they are used for noticeably different things. Diphenhydramine is an over-the-counter allergy medicine and sleep aid with a short duration, a few hours. Hydroxyzine lasts much longer, is prescription-only in most countries, and is used for anxiety and itching as well as allergy, partly because it also acts on serotonin receptors. Hydroxyzine is the heavier molecule at 374.9 against 255.35 and carries a piperazine ring where diphenhydramine has a simple dimethylamine. Cetirizine, the common non-drowsy antihistamine, is actually hydroxyzine's own metabolite with that ring capped by a carboxylic acid.

Side by side

Common questions

What is the difference between Hydroxyzine and Diphenhydramine?

Both are first generation antihistamines that cross into the brain and cause drowsiness, and they are used for noticeably different things. Diphenhydramine is an over-the-counter allergy medicine and sleep aid with a short duration, a few hours. Hydroxyzine lasts much longer, is prescription-only in most countries, and is used for anxiety and itching as well as allergy, partly because it also acts on serotonin receptors.

Is Hydroxyzine bigger than Diphenhydramine?

Hydroxyzine is the heavier molecule, 374.9 g/mol against 255.35 g/mol for Diphenhydramine. Hydroxyzine is C21H27ClN2O2 and Diphenhydramine is C17H21NO.

Which has the lower reported LD50, Hydroxyzine or Diphenhydramine?

Diphenhydramine, at 500 mg/kg (oral, rat), against 840 mg/kg (oral, rat) for Hydroxyzine. An LD50 is one acute animal measurement, and the two here were not necessarily measured in the same species, so it is a data point rather than a ranking of how dangerous either is to a person.