1-What is the physiological role of histamine? Histamine is a biogenic amine involved in local immune responses, as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. It increases the permeability of capillaries to white blood cells and other proteins, to allow them to engage foreign invaders in affected tissues. It is found in virtually all cells of the animal body2-How is histamine synthesized within the body?In L-hsitidine decarboxylase, histamine is synthesized by decarboxylation of the amino acid histidine.3-Provide a brief description of the therapeutic applications of histamine H1, H2 and H3 receptor antagonists. H1 receptor antagonists are usually the first-line treatment given for seasonal allergic rhinitis. H2 antagonists have helped many patients with gastrointestinal disorders in attenuating gastric acid secretion. The H3 antagonist can be aided in the treatment of the sleep-wake cycle. and in memory formation and alertness.4- Where are H4 receptors predominantly expressed?The histamine H4 receptor (H4R) is predominantly expressed on cells of the immune system5- What is the main defect associated with the prototypical H4 antagonist of 'histamine JNJ7777120? It has a short half-life due to rapid demethylation of the terminal N-methyl piperazine,6- How might the weakness associated with JNJ manifest itself in terms of pharmacokinetics and pharmacology? It can be seen that the weakness of JNJ is associated with its short half-life due to its high clearance and rapid metabolization.7- When describing the properties of JNJ 40279486, the authors highlight the selectivity of the compound towards the hERG channel. Explain which...... half of the paper ...... titrated in nitrogen (primary)19- On what basis was compound 5 selected as a clinical candidate despite 31 and what was proposed as a possible reason for the superiority of 5. Because 5 showed an increased pharmacodynamic effect in inhibiting LPS-induced TNFα release. Furthermore, compound 5 showed inhibition when the plasma concentration was at or above the mouse Ki, while 31 had plasma concentrations above the mouse Ki. The following figure demonstrates this fact. Additionally, compound 5 had a significantly higher volume of distribution than compound 31.20-There are at least 3 typographical errors in the document. Two are in Table 1 and one in the section titled In Vivo Profiling of Lead Molecules. Identify one of these typographical errors. One of the typographical errors in the document is hki and it must be Ki