Category: receptor_pharmacology
Histamine acts at four GPCRs: H1 (Gq, allergic + bronchoconstriction + CNS arousal — H1-i causes sedation), H2 (Gs, gastric acid — covered in GI-1), H3 (presynaptic autoreceptor in CNS), H4 (immune cells, chemotaxis). First-gen H1 blockers cross BBB → sedation (diphenhydramine, hydroxyzine, doxylamine, chlorpheniramine, brompheniramine, meclizine, dimenhydrinate, promethazine). Second-gen H1 blockers minimize BBB penetration → non-sedating (loratadine, cetirizine, desloratadine, fexofenadine, levocetirizine, ketotifen, olopatadine — last two also have mast-cell-stabilizer activity for ophthalmic use). Inverse agonism at H1 + strong anticholinergic side effects characterize the first-generation class. Cetirizine + levocetirizine retain mild BBB penetration → some sedation.