Pathways

Temocapril is an angiotensin-converting enzyme (ACE) inhibitor for the conversion of angiotensin I into angiotensin II. It is approved in Japan and South Korea but not in the United States. Angiotensin II is a critical circulating peptide hormone that has powerful vasoconstrictive effects and increases blood pressure. Temocapril is used to treat hypertension, high blood pressure, congestive heart failure, and chronic renal failure as it decreases blood pressure. Temocapril is converted into Temocaprilat through the liver after being ingested which travels in the blood to inhibit ACE which is from the lungs. Angiotensin has many vasoconstrictive effects by binding to angiotensin II type 1 receptor (AT1) in blood vessels, kidneys, hypothalamus, and posterior pituitary. In blood vessels, AT1 receptors cause vasoconstriction in the tunica media layer of smooth muscle surrounding blood vessels increasing blood pressure. Less angiotensin II that is circulating lowers the constriction of these blood vessels. AT1 receptors in the kidney are responsible for the production of aldosterone which increases salt and water retention which increases blood volume. Less angiotensin II reduces aldosterone production allowing water retention to not increase. AT1 receptors in the hypothalamus are on astrocytes which inhibit the excitatory amino acid transporter 3 from up-taking glutamate back into astrocytes. Glutamate is responsible for the activation of NMDA receptors on paraventricular nucleus neurons (PVN neurons) that lead to thirst sensation. Since angiotensin II levels are lowered, the inhibition of the uptake transporter is not limited decreasing the amount of glutamate activating NMDA on PVN neurons that make the individual crave drinking less. This lowers the blood volume as well. Lastly, the AT1 receptors on posterior pituitary gland are responsible for the release of vasopressin. Vasopressin is an anti-diuretic hormone that cases water reabsorption in the kidney as well as causing smooth muscle contraction in blood vessels increasing blood pressure. Less angiotensin II activating vasopressin release inhibits blood pressure from increasing. Overall, Temocapril inhibits the conversion of angiotensin I into angiotensin II, a powerful vasoconstrictor and mediator of high blood pressure so decreasing levels of angiotensin will help reduce blood pressure from climbing in individuals.

Temocapril (trade name: Acecol) belongs to the class of drugs known as angiotensin-converting enzyme (ACE) inhibitors and is used primarily to lower high blood pressure (hypertension). This drug can also be used in the treatment of congestive heart failure and type II diabetes. Temocapril is a prodrug which, following oral administration, undergoes biotransformation in vivo into its active form temocaprilat via cleavage of its ester group by the liver. Angiotensin-converting enzyme (ACE) is a component of the body's renin–angiotensin–aldosterone system (RAAS) and cleaves inactive angiotensin I into the active vasoconstrictor angiotensin II. ACE (or kininase II) also degrades the potent vasodilator bradykinin. Consequently, ACE inhibitors decrease angiotensin II concentrations and increase bradykinin concentrations resulting in blood vessel dilation and thereby lowering blood pressure.

Temocapril (trade name: Acecol) belongs to the class of drugs known as angiotensin-converting enzyme (ACE) inhibitors and is used primarily to lower high blood pressure (hypertension). This drug can also be used in the treatment of congestive heart failure and type II diabetes. Temocapril is a prodrug which, following oral administration, undergoes biotransformation in vivo into its active form temocaprilat via cleavage of its ester group by the liver. Angiotensin-converting enzyme (ACE) is a component of the body's renin–angiotensin–aldosterone system (RAAS) and cleaves inactive angiotensin I into the active vasoconstrictor angiotensin II. ACE (or kininase II) also degrades the potent vasodilator bradykinin. Consequently, ACE inhibitors decrease angiotensin II concentrations and increase bradykinin concentrations resulting in blood vessel dilation and thereby lowering blood pressure.

Temozolomide (TMZ) is an antineoplastic from the alkylating agent drug class. This molecule is an imidazotetrazine prodrug that is stable at acidic pH but undergoes spontaneous nonenzymatic hydrolysis at neutral or slightly basic pH; allowing its administration to be oral and intravenous too. Temozolomide is indicated in the treatment of newly diagnosed glioblastoma and refractory anaplastic astrocytoma. This molecule is a very small lipophilic, it can then easily get through the blood-brain barrier. The mechanism of action of this drug needs many reactions beforehand: TMZ undergoes spontaneous nonenzymatic breakdown at physiological pH to form 5-(3-methyltriazen-1-yl) imidazole-4-carboxamide (MTIC), which then reacts with water to produce 5-aminoimidazole-4-carboxamide (AIC) and a highly reactive methyl diazonium cation. TMZ is a bit specific to tumor cells because glioblastoma typically possesses a more alkaline pH than healthy tissue, favoring its activation in tumor cells. The methyl diazonium cation formed methylates DNA at the N7 and O6 position of guanine, and the N3 position of adenine. The cellular repair system will eventually lead to DNA strand breaks that will end in the apoptosis of the cell.

Template PIS1M1, Template PIS1M2, Template PIS1M3,Template PIS1M4, Template PIS2M1, Template PIS2M2, Template PIS2M3 are metabolites of Template predicted with biotransformer. Template M1, Template M2, Template M3, Template M4, Template M5, Template M6, Template M7, Template M8, Template M9, Template M10, Template M11, Template M12, Template M13, Template M14, Template M15, Template M16, Template M17, Template M18 are metabolites of Template predicted with biotransformer.