Pathways

Tranylcypromine is a non-hydrazine monoamine oxidase inhibitor belonging to the class of antidepressants called MAOIs. This drug is indicated in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in panic and phobic disorders. The monoamine oxidase is an enzyme that catalyzes the oxidative deamination of many amines like serotonin, norepinephrine, epinephrine, and dopamine. There are 2 isoforms of this protein: A and B. The first one is found in cells located in the periphery and breakdown serotonin, norepinephrine, epinephrine, dopamine, and tyramine. The second one, the B isoform, breakdowns phenylethylamine, norepinephrine, epinephrine, dopamine, and tyramine. This isoform is found in the extracellular tissues and mostly in the brain. The mechanism of action of the MAOIs is still not determined, it is thought that they act by increasing free serotonin and norepinephrine concentrations and/or by altering the concentrations of other amines in the CNS. MAO A inhibition is thought to be more relevant to antidepressant activity than the inhibition caused by MAO B. Selective MAO B inhibitors have no antidepressant effects. An overdose of this drug will result in insomnia, restlessness, and anxiety. Hypotension, dizziness, weakness, and drowsiness may occur, progressing in severe cases to extreme dizziness and shock. This drug is administered as an oral tablet.

Tranylcypromine is a non-hydrazine monoamine oxidase inhibitor belonging to the class of antidepressants called MAOIs. This drug is indicated in the treatment of major depression, dysthymic disorder, and atypical depression. It also is useful in panic and phobic disorders. The monoamine oxidase is an enzyme that catalyzes the oxidative deamination of many amines like serotonin, norepinephrine, epinephrine, and dopamine. There are 2 isoforms of this protein: A and B. The first one is found in cells located in the periphery and breakdown serotonin, norepinephrine, epinephrine, dopamine, and tyramine. The second one, the B isoform, breakdowns phenylethylamine, norepinephrine, epinephrine, dopamine, and tyramine. This isoform is found in the extracellular tissues and mostly in the brain. The mechanism of action of the MAOIs is still not determined, it is thought that they act by increasing free serotonin and norepinephrine concentrations and/or by altering the concentrations of other amines in the CNS. MAO A inhibition is thought to be more relevant to antidepressant activity than the inhibition caused by MAO B. Selective MAO B inhibitors have no antidepressant effects. An overdose of this drug will result in insomnia, restlessness, and anxiety. Hypotension, dizziness, weakness, and drowsiness may occur, progressing in severe cases to extreme dizziness and shock. This drug is administered as an oral tablet.

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

Trastuzumab is a recombinant humanized IgG1 monoclonal antibody to the human epidermal growth factor receptor 2 (HER2) that is administered intravenously for the treatment of HER2 positive breast cancer (adjuvant therapy), metastatic HER2-positive breast cancer and HER2 positive gastric cancer. HER-2 is over expressed in these cancer cells and therefore trastuzumab targets these cancer cells over normal cells. The HER-2 receptor is a transmembrane tyrosine kinase receptor that consists of an extracellular ligand-binding domain, a transmembrane region, and an intracellular or cytoplasmic tyrosine kinase domain. HER-2 forms heterodimers with other EGFR proteins such as HER-1, HER-2 or HER-4 when they bind to ligands or may form homodimers with other HER-2 proteins. Following dimerization, transphosphorylation/ autophosphorylation of the tyrosine residues on the cytoplasmic domain of these receptors occurs. This activates a number of intracellular signaling pathways such as the raf/MAPK pathway, PI3K/akt pathway and PLC/PKC pathway. The activation of these pathways recruits nuclear factors that regulate genes involved in cell-cycle progression, proliferation, growth and survival. Trastuzumab binds to the extracellular domain of HER-2 and prevents dimerization. Inhibiting dimerization prevents the activation of the downstream intracellular signaling cascades initiated by the HER proteins. This therefore prevents the gene regulation necessary to promote cell-cycle progression, proliferation, growth and survival. Nuclear transcription affected by these pathways cannot occur, and therefore essential proteins are not produced. This causes cell cycle arrest and suppresses cell growth and proliferation and eventually the cancer cell undergoes apoptosis. Side effects such as headache, chills, cough, back pain, weakness and fatigue, upper respiratory symptoms including rhinitis and pharyngitis, angioedema, cardiotoxicity, anaphylaxis and GI disturbances including nausea, vomiting, abdominal pain, diarrhea.

Trastuzumab is an anti-EGFR drug used in the treatment of HER2-positive breast cancer. EGFR is linked multiple signalling pathways involved in tumour growth and angiogenesis such as the Ras/Raf pathway and the PI3K/Akt pathways. These pathways ultimately lead to the activation of transcription factors such as Jun, Fos, and Myc, as well as cyclin D1, which stimulates cell growth and mitosis. Uncontrolled cell growth and mitosis leads to cancer. Trastuzumab acts as an anticancer drug by binding to the extracellular domain of the EGFR and preventing its activation by epidermal growth factor. This in turn inhibits downstream signalling and prevents tumour growth.

Travoprost is a prostaglandin E1 analog that reduces the risk of NSAID-induced gastric ulcers. Travoprost stimulates prostaglandin receptors on parietal cells in the stomach to reduce gastric acid secretion. Travoprost activates prostaglandin EP3 receptors in parietal cells. Activation of this receptor triggers the Gi protein signaling cascade, inhibiting adenylate cyclase. Adenylate cyclase is responsible for converting ATP to cAMP, therefore, inhibition of adenylate cyclase reduces cytosolic cAMP concentration. cAMP is responsible for activating protein kinase A. With lower concentrations of cAMP, less protein kinase A is activated. Protein kinase A activates the proton pump in the luminal membrane of the parietal cell. The role of the proton pump is to secrete acid (H+) into the stomach lumen. With reduced protein kinase A activation, this decreases the activity of the proton pump, fewer H+ ions are pumped into the lumen, reducing the acidity and thus allowing stomach ulcers to heal and reducing the pain caused by the ulcers. Travoprost may also promote ulcer healing by increasing mucus and bicarbonate secretion and thickening the mucosal bilayer so the mucosa can generate new cells.

Metabolites of Travoprost are predicted with biotransformer.