Which of the following antihistamines is known to cause significant sedation?

Diphenhydramine is known to cause significant sedation due to its properties as a first-generation antihistamine. First-generation antihistamines readily cross the blood-brain barrier and have anticholinergic effects, which can lead to drowsiness. This sedative effect is often leveraged therapeutically to aid sleep or manage allergies in instances where daytime alertness is not a priority.

In contrast, the other antihistamines listed are classified as second-generation antihistamines, such as fexofenadine, cetirizine, and loratadine. These medications are designed to be less sedating as they are less likely to penetrate the central nervous system. While cetirizine can cause some sedation in a subset of patients, it generally does not compete with the level of sedation associated with diphenhydramine. The key distinguishing feature of diphenhydramine is its more pronounced side effect profile related to sedation, making it the correct answer in this context.