Tust Techasith11-30-04Medicinal ChemistryDr. John Buynak.ppt

* Tust Techasith 11-30-04 Medicinal Chemistry Dr. John Buynak “markedly improved susceptibility to a specific protein after a suitable incubation period” -- Charles Richet, 1902 Current definition: sudden, severe, potentially fatal, systemic allergic reaction that can involve various areas of the body (such as the skin, respiratory tract, gastrointestinal tract, and cardiovascular system). Common cause: Food, Insect stings, Medicines, Latex Richert believed that this condition was due to the protein poisonous in nature and that after the first exposure, the body’s defense against the poison is weakened. Clemens von Pirquet “thought that the first injection in some way changed the reaction of the body so that it became hypersensitive to the second injection of the same material” Sir Henry Dale, discovered histamine He performed an experiment that shows that the injection of foreign protein, allergen, causes smooth muscle contraction. He then proposed that the endogenous protein histamine plays a role in this process; he proved it using two experiments. First, he showed that an injection of histamine causes lung contractions in guinea pigs. He then shows that allergens induce the release of histamine protein in dogs and guinea pigs in a sufficient quantity to cause the symptoms of allergy. “histamine mediates the allergic symptoms by binding to some receptor of histamine on the cell” NH3+ --- COO- Aspartate Nucleophilic N(3) 929F: Toxic RP2339: The first compound that was used to treat human clinically. H1, H2, H3, H4: All GPCR’s H1: brain, smooth muscle from airways, gastrointestinal (GI) tract, genitourinary system, the cardiovascular system, adrenal medulla, and endothelial cells, and lymphocytes. Target of Antihistamines “compete against the receptors’ natural substrate, histamine, in binding to the receptors “ The aryl groups are usually substituted and the substitution is shown to play a role in the activity an