Pathways

Tritoqualine is an H1-antihistamine. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Reducing the activity of the NF-κB immune response transcription factor through the phospholipase C and the phosphatidylinositol (PIP2) signalling pathways also decreases antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Furthermore, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release. First-generation antihistamines readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects (e.g. nervousness and insomnia). Second-generation antihistamines are more selective for H1-receptors of the peripheral nervous system (PNS) and do not cross the blood-brain barrier. Consequently, these newer drugs elicit fewer adverse drug reactions.

Triterpenoids have 30 carbons and six isoprene units. They are derived from (S)-2,3-epoxysqualene. They may contain rings or be acyclic, depending on the bonds formed by the loss of the diphosphate group. First, the terpenoid backbone is synthesized, producing farnesyl pyrophosphate. Two molecules of farnesyl pyrophosphate then join together to form presqualene diphosphate, catalyzed by squalene synthase 1. Then, the same enzyme removes the pyrophosphate group and replaces it with a hydrogen ion, forming squalene. Squalene then undergoes oxidation of one of its bonds via squlene monooxygenase 1, to form (S)-2,3-epoxysqualene. This may then proceed to the steroid biosynthesis pathway or may react with an isomerase or lyase to form a chair-chair-chair-boat triterpenoid. Similarly, squalene may interact with an isomerase or lyase to form a chair-chair-chair-chair triterpenoid. After the backbone is complete, (S)-2,3-epoxysqualene can interact with many enzymes in order to form the triterpenoids. It can interact with camelliol C synthase to form camelliol C, thalianol synthase to form thalianol, baruol synthase to form baruol, tirucalladienol synthase to form tirucalla-7,24-dien-3-beta-ol, amyrun synthase LUP2 to form lupeol, alpha- and beta-amyrin synthases to form alpha- and beta-amyrin respectively. It can also interact with lupan-3beta,20-diol synthase to add a water molecule to form lupan-3beta,20-diol, alpha- and beta-seco-amyrin synthases to form alpha- and beta-seco-amyrin respectively, marneral synthase to form marneral, and finally arabidiol synthase to add a water molecule and form arabidiol.

Gadoversetamide is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Gadoversetamide passes through the liver and is then excreted from the body mainly through the kidney.

Choline magnesium trisalicylate (trisalicylate-choline) is a non-acetylated salicylate used widely as a nonsteroidal anti-inflammatory drug. It is used to reduce pain and inflammation caused by conditions such as arthritis. This medication is also used to treat fever in adults. It targets the prostaglandin G/H synthase-1 (COX-1) and prostaglandin G/H synthase-2 (COX-2) in the cyclooxygenase pathway. The cyclooxygenase pathway begins in the cytosol with phospholipids being converted into arachidonic acid by the action of phospholipase A2. The rest of the pathway occurs on the endoplasmic reticulum membrane, where prostaglandin G/H synthase 1 & 2 converts arachidonic acid into prostaglandin H2. Prostaglandin H2 can either be converted into thromboxane A2 via thromboxane A synthase, prostacyclin/prostaglandin I2 via prostacyclin synthase or prostaglandin E2 via prostaglandin E synthase. COX-2 is an inducible enzyme, and during inflammation, it is responsible for prostaglandin synthesis. It leads to the formation of prostaglandin E2 which is responsible for contributing to the inflammatory response by activating immune cells and for increasing pain sensation by acting on pain fibers. Trisalicylate-choline inhibits the action of COX-1 and COX-2 on the endoplasmic reticulum membrane. This reduces the formation of prostaglandin H2 and therefore, prostaglandin E2 (PGE2). The low concentration of prostaglandin E2 attenuates the effect it has on stimulating immune cells and pain fibers, consequently reducing inflammation and pain. Fever is triggered by inflammatory and infectious diseases. Cytokines are produced in the central nervous system (CNS) during an inflammatory response. These cytokines induce COX-2 production that increases the synthesis of prostaglandin, specifically prostaglandin E2 which adjusts hypothalamic temperature control by increasing heat production. Because trisalicylate-choline decrease PGE2 in the CNS, it has an antipyretic effect.

Trisalicylate-Choline (also named Choline Magnesium Trisalicylate) is a nonsteroidal anti-inflammatory drug (NSAID). It can be used to treat pain and fever. Trisalicylate-Choline can block prostaglandin synthesis by the action of inhibition of prostaglandin G/H synthase 1 and 2. Prostaglandin G/H synthase 1 and 2 catalyze the arachidonic acid to prostaglandin G2, and also catalyze prostaglandin G2 to prostaglandin H2 in the metabolism pathway. Decreased prostaglandin synthesis in many animal model's cell is caused by presence of trisalicylate-choline.

Metabolites of Triprolidine are predicted with biotransformer.

Triprolidine is a first-generation ethanolamine H1-antihistamine. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Reducing the activity of the NF-κB immune response transcription factor through the phospholipase C and the phosphatidylinositol (PIP2) signalling pathways also decreases antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Furthermore, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release. First-generation antihistamines readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects (e.g. nervousness and insomnia). Second-generation antihistamines are more selective for H1-receptors of the peripheral nervous system (PNS) and do not cross the blood-brain barrier. Consequently, these newer drugs elicit fewer adverse drug reactions.