Pathways

Terfenadine is a second-generation piperidine 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.

Terfenadine is an antihistamine for the treatment of allergy symptoms. 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. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. Allergies causes blood vessel dilation which causes swelling (edema) and fluid leakage. Terfenadine inhibits the H1 histamine receptor on blood vessel endothelial cells. This normally activates the Gq signalling cascade which activates phospholipase C which catalyzes the production of Inositol 1,4,5-trisphosphate (IP3) and Diacylglycerol (DAG). Because of the inhibition, IP3 doesn't activate the release of calcium from the sarcoplasmic reticulum, and DAG doesn't activate the release of calcium into the cytosol of the endothelial cell. This causes a low concentration of calcium in the cytosol, and it, therefore, cannot bind to calmodulin. Calcium bound calmodulin is required for the activation of the calmodulin-binding domain of nitric oxide synthase. The inhibition of nitric oxide synthesis prevents the activation of myosin light chain phosphatase. This causes an accumulation of myosin light chain-phosphate which causes the muscle to contract and the blood vessel to constrict, decreasing the swelling and fluid leakage from the blood vessels caused by allergens.

Terfenadine is an antihistamine for the treatment of allergy symptoms. 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. H1-antihistamines act on H1 receptors in T-cells to inhibit the immune response, in blood vessels to constrict dilated blood vessels, and in smooth muscles of lungs and intestines to relax those muscles. 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.

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

Terpenoids are a class of organic compounds made up of 5 carbon isoprene units. There are two pathways, melvalonate and MEP/DOXP, that synthesize the terpenoid backbone components. Both of these create isopentenyl pyrophosphate, which may then react using isopentenyl diphosphate isomerase in the chloroplast to form dimethylallylprophosphate. This molecule is also produced by the MEP/DOXP pathway. Isopentenyl pyrophosphate and dimethylallylprophosphate can react with geranylphosphate synthase in the mitochondrion to form geranyl-pyrophosphate, the main compound used in monoterpenoid biosynthesis. Geranyl-pyrophosphate may also react again with isopentenyl pyrophosphate using solanesyl diphosphate synthase 2 in the chloroplast to form solanesyl pyrophosphate, a potential end product of this pathway. Alternately, they can react with (2E,6E)-farnesyl diphosphate synthase, also in the mitochondrion, to form farnesyl phosphate. Farnesyl pyrophosphate may then be used as the main precursor in the sesquiterpenoid and triterpenoid biosynthesis pathways. It may also react with geranylgeranyl pyrophosphate 6 in the mitochondrion to form geranylgeranyl pyrophosphate. Geranylgeranyl pyrophosphate can react with isopentenyl pyrophosphate, catalyzed by solanesyl diphosphate syntahse 2, again in the chloroplast, to form solanesyl pyrophosphate. Aside this reaction, it can be converted by geranylgeranyl dehydrogenase in the chloroplast to form phytyl pyrophosphate, another end product of this pathway. Farnesyl pyrophosphate can additionally react using an undecaprenyl pyrophosphate synthetase family protein as a catalyst in order to form dehydrolichol pyrophosphate, or with the protein farnesyltransferase complex, which will add a protein-cysteine to the farnesyl pyrophosphate, which in turn loses its pyrophosphate group. The S-farnesyl protein then reacts with either CAAX prenyl protease 1 or 2 in the endoplasmic reticulum membrane to form protein C-terminal S-farnesyl-L-cysteine. This complex then reacts using protein-S-isoprenylcysteine O-methyltransferase B, still in the endoplasmic reticulum membrane, to form protein-C-terminal S-farnesyl-L-cysteine methyl ester. This reaction may be reversed by isoprenylcysteine alpha-carbonyl methylesterase, yet again in the endoplasmic reticulum membrane. Alternately, through an as of yet unknown reaction, the protein may be removed, as well as several other structure changes, leaving farnesylcysteine. In the lysosome, farnesylcysteine can be catalyzed by farnesylcysteine to remove the cysteine group, leaving behind farnesal. Then, a NAD-binding Rossman-fold superfamily protein can catalyze its transformation into farnesol. Finally, within the chloroplast, farnesol can be catalyzed by farnesol kinase to form farnesyl phosphate, the final product of this pathway.

From glycolysis and the mevalonate pathway, diphosphomevalonic acid can be reacted with ATP to produce isopentenyl diphosphate which can be used in many reactions due to it's phosphate groups. Isopentenyl can be converted into geranyl pyrophosphate through two different paths, with one having an intermediate of dimethylallylpyrophosphate. Geranyl pyrophosphate itself can be used in monoterpenoid biosynthesis but more importantly, it can converted into (E,E)- farnesyl diphosphate through farnesyl pyrophosphate synthase. With (E,E)-farnesyl diphosphate and isopentenyl diphosphate, many reactions can take place depending on the number of substrates are used and how many phosphate groups are to be transferred. The products from the reactions are usually substrates for other biosynthesis pathways like N-glycan biosynthesis, carotenoid biosynthesis, diterpenoid biosynthesis, steroid biosynthesis and ubiquinone and other terpenoid quinone biosynthesis pathways. (E,E) farnesyl diphosphate can also be combined with a cysteine protein to make S-farnesyl protein. S-Farnesyl protein can have the c-terminal removed and then can be trans methylated by S-adenosylmethionine to eventually make farnesylcysteine. Through unknown processes farnesylcysteine can be converted can converted back to (E,E) farnesyl diphosphate, but not all the enzymes are known yet.

The biosynthesis of steroids begins with acetyl coa being turned into acetoacetyl through a acetoacetyl CoA thiolase. Acetoacetyl -CoA reacts with an acetyl-CoA and water through a 3-hydroxy 3-methylglutaryl coenzyme A synthase resulting in the release of coenzyme A, hydrogen ion and (S)-3-hydroxy-3-methylglutaryl-CoA. The latter compound reacts with NADPH and a hydrogen ion through a 3-hydroxy-3-methylglutaryl-coenzyme A resulting in the release of coenzyme A , NADP and mevalonate. Mevalonate is then phosphorylated through an ATP driven kinase mevalonate kinase resulting in the release of ADP, hydrogen ion and mevalonate 5-phosphate. The latter compound is phosphorylated through an ATP driven kinase, phosphomevalonate kinase resulting in the release of ADP and mevalonate diphosphate. This latter compound then reacts with an ATP driven mevalonate diphosphate decarboxylase resulting in the release of ADP, carbon dioxide, a phosphate and a isopentenyl diphosphate. The latter compound can be isomerized into dimethylallyl diphosphate or reacth with a dimethylallyl diphosphate to produce geranyl diphosphate. Geranyl diphosphate reacts with a isopentenyl through a farnesyl diphosphate synthase resulting in the release of diphosphate and farnesyl diphosphate. Farnesyl diphosphate has three different fates: 1.-Producing hexaprenyl diphosphate in the mitocondrial inner membrane by reacting with 3 isopentenyl diphosphate 2.-Producing geranylgeranyl diphosphate in the cytoplasm by reacting with one isopentenyl diphosphate 3.-Producing a dolichol precursor in the ER by reacting with 13 isopentenyl diphosphates.