MedicinalChemistryChapter3.ppt

* 从胃肠吸收, 在肠壁和肝代谢, 4-O-glucuronide mostly metabolised in dog, rabbit and rat While for human, 4-O-sulfate Loratadine 氯雷他定 4- 8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridine-11-ylidene -piperidine carboxylic acid ethyl ester Metabolism desloratadine Metabolite : desloratadine is potent antagonism of hismtamine H1 Receptor. It was launched as new drug in 2001. Second generation of antihistamine: also called second generation nonsedating H1 antihistamines. Potent effect, prolonged action, etc. No antiadrenergic and anticholinergic effects, no CNS depression. Relieves symptoms of allergic rhinitis, such as, itchy 痒 , sneezing 喷嚏 ; and runny nose. Action and Use Cetirizine Hydrochloride 盐酸西替利嗪 ? -2-[2-[4-[ 4-Chlorophenyl phenylmethyl]piperazin-1-yl]ethoxy]acetic acid dihydrochloride Action and Use Second Generation Antihistamines: Little antiadrenergic and anticholinergic effects No CNS depression No reported cardiac side effect Effective against rash/hives 皮疹/荨麻疹 Mizolastine 咪唑斯汀 2-[[1-[1-[ 4-Fluorophenyl methyl]-1H-benzimidazol-2-yl-4-piperidinyl]methylamino]-4 1H -pyrimidinone Action and Use Second Generation Antihistamine Have both antihistamine and inhibition of mediators of inflammation, and no reported cardiac side effect, better than other second generation antihistamines. Fast onset, potent and prolonged effects. 2. The principal metabolic pathway is glucuronidation of the parent compound. 3. Relief of seasonal allergic rhinitis and urticaria. Structural features Features of three generation antihistamines The first genetation antihistamines have effects at cholinergic, adrenergic, dopaminergic and serotonergic receptors. The most common side effect of these agents is CNS depression including sedation, drowsiness, etc. The second generation antihistamines have improved H1 receptor selectivity, little or no sedative qualities, and the antihistamines have been called second genetation nonsedating H1 antihistamines e.g., loratadin