Jawaharlal Nehru Technological University Hyderabad B.Pharmacy IV MEDICINAL CHEMISTRY-II Previous Question Paper (September-2021 - R17)

Histamine receptors are G-protein coupled receptors (GPCRs) that mediate the physiological effects of histamine. There are four primary subtypes, H1, H2, H3, and H4, each with distinct distributions and signaling pathways:

• H1 receptors: Primarily located in smooth muscles of the bronchi and gut, vascular endothelial cells, and the central nervous system. Activation leads to vasodilation, increased capillary permeability, bronchoconstriction, and wakefulness.
• H2 receptors: Predominantly found in the gastric parietal cells, cardiac muscle, and vascular smooth muscle. Their primary function is the stimulation of gastric acid secretion and positive chronotropic effects on the heart.
• H3 receptors: Located primarily in the central nervous system (presynaptic nerve terminals) and to a lesser extent in the peripheral nervous system. They function as autoreceptors to inhibit the release of histamine and other neurotransmitters like acetylcholine and norepinephrine.
• H4 receptors: Primarily expressed on hematopoietic cells, including mast cells, eosinophils, and T-lymphocytes. They play a significant role in chemotaxis and the mediation of inflammatory responses.

H1-antagonists are classified based on their chemical structure into the following groups: 1) Ethanolamine ethers (e.g., Diphenhydramine), 2) Ethylenediamines (e.g., Mepyramine), 3) Alkylamines (e.g., Chlorpheniramine), 4) Piperazines (e.g., Cyclizine), 5) Phenothiazines (e.g., Promethazine), and 6) Piperidines (e.g., Fexofenadine).

The synthesis of Diphenhydramine hydrochloride involves the reaction of benzhydryl bromide with 2-dimethylaminoethanol in the presence of a base:

The resulting diphenhydramine base is then treated with hydrochloric acid to form the stable salt, Diphenhydramine hydrochloride.