diphenhydramine UK /ˌdʌɪ.fɛnˈhʌɪ.dɹəm.iːn/US /ˌdaɪˌfɛnˈhaɪ.dɹəˌmiːn/ noun1 •An antihistamine and anticholinergic drug that blocks the effect of histamine at H₁ receptor sites, relieving allergy symptoms. It also reduces smooth muscle contraction, increases heart rate, and sedates the user by blocking muscarinic acetylcholine receptors (mAChRs).Diphenhydramine is a convenient and cheap antihistamine for use, but there are other drugs that do not make the user tired. formsdiphenhydramines