Loratadine vs Diphenhydramine: what is the difference?

How they differ

This is the Claritin and Benadryl comparison, and it is the clearest example of what separates antihistamine generations. Diphenhydramine is a small, fat-soluble first generation molecule that crosses into the brain easily, which is why it works within an hour and reliably causes drowsiness, and why it doubles as a sleep aid. Loratadine is built to stay out of the brain, so it is non-sedating for most people, but it lasts a full day where diphenhydramine's effect fades in a few hours. Diphenhydramine also blocks acetylcholine receptors, which is where the dry mouth and blurred vision come from, and loratadine largely does not. Loratadine is much the heavier molecule at 382.9 against 255.35.

Side by side

Common questions

What is the difference between Loratadine and Diphenhydramine?

This is the Claritin and Benadryl comparison, and it is the clearest example of what separates antihistamine generations. Diphenhydramine is a small, fat-soluble first generation molecule that crosses into the brain easily, which is why it works within an hour and reliably causes drowsiness, and why it doubles as a sleep aid. Loratadine is built to stay out of the brain, so it is non-sedating for most people, but it lasts a full day where diphenhydramine's effect fades in a few hours.

Is Loratadine bigger than Diphenhydramine?

Loratadine is the heavier molecule, 382.9 g/mol against 255.35 g/mol for Diphenhydramine. Loratadine is C22H23ClN2O2 and Diphenhydramine is C17H21NO.

Which has the lower reported LD50, Loratadine or Diphenhydramine?

Diphenhydramine, at 500 mg/kg (oral, rat), against 5,000 mg/kg (oral, rat) for Loratadine. 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.