Structure
Diphenhydramine hydrochloride is a first-generation antihistamine characterized by two phenyl rings connected by an ethylamine chain.
The chemical structure includes:
Two benzene rings (diphenyl)
An ether linkage (-O-) between them
An ethyl chain ending with a dimethylamino group
Protonated hydrochloride salt form
Chemical Formula: C₁₇H₂₁NO·HCl
Structure of Diphenhydramine hydrochloride
Mode of Action
Diphenhydramine acts as a competitive antagonist at H₁-receptors. I
t crosses the blood-brain barrier, leading to central nervous system (CNS) effects such as sedation. Additionally, it exhibits anticholinergic and antiemetic properties.
Uses
Allergic rhinitis
Urticaria (hives)
Common cold symptoms
Motion sickness (in combination with other agents like in Dimenhydrinate)
Insomnia
Cough suppressant (in some formulations)
Structure-Activity Relationship (SAR)
Aromatic Rings: The two phenyl rings enhance lipophilicity, facilitating crossing the blood-brain barrier, contributing to sedative effects.
Ethylene Bridge: Provides the necessary flexibility for receptor binding.
Dimethylamino Group: Essential for H₁ receptor antagonism; the basic nitrogen forms hydrogen bonds with the receptor.
Hydroxyl Groups: Presence in related structures can modify lipophilicity and metabolism.
Synthesis of Diphenhydramine hydrochloride
Diphenhydramine can be synthesized via the Reimer-Tiemann reaction:
1. Starting Materials: Diphenylmethanol and dimethylamine.
2. Formation of Intermediate: Diphenylmethanol reacts with dimethylamine to form diphenylmethyl dimethylamine.
3. Alkylation: The intermediate is alkylated with appropriate alkylating agents to introduce the ethylene bridge.
4. Salt Formation: Finally, the free base is converted to its hydrochloride salt using hydrochloric acid.