Pathways

Remoxipride is an atypical antipsychotic dopamine D2 antagonist. Chronic use upregulates the expression of D2 receptors, while downregulating the expression of D1 and D5 receptors in the prefrontal cortex. This activity may be related to the antipsychotic activity of remoxipride. Remoxipride displays weaker binding to D2 dopaminergic receptors that dopamine. This weaker binding is thought to account for the reduced incidence of Parkinsonism. Remoxipride also increases expression of the protein Fos in the nucleus accumbens but not the dorsolateral striatum, which may be responsible for a reduced incidence of extrapyramidal symptoms.

Metabolites of Remoxipride are predicted with biotransformer.

Repaglinide is rapidly metabolized via oxidation and dealkylation by cytochrome P450 3A4 and 2C9 to form the major dicarboxylic acid derivative (M2). Further oxidation produces the aromatic amine derivative (M1). Glucuronidation of the carboxylic acid group of repaglinide yields an acyl glucuronide (M7). Several other unidentified metabolites have been detected. Repaglinide metabolites to not possess appreciable hypoglycemic activity. (DrugBank)

Repaglinide is a non-sulfonylurea insulin secretagogue used in the treatment of type 2 diabetes. As the name of the drug class suggests, repaglinide acts on pancreatic beta-cells to stimulate insulin secretion. Under physiological conditions, insulin secretion from beta-cells is mediated by elevated glucose concentration in the blood. Glucose enters the cell via GLUT2 (SLC2A2) transporters. Once inside the cell, glucose is metabolized to produce ATP. High concentration of ATP will inhibit ATP-dependent potassium channels (ABCC8), which depolarizes the cell. Depolarization causes opening of voltage-gated calcium channels, allowing calcium to enter cell. High intracellular calcium subsequently stimulate vesicle exocytosis and insulin secretion. Repaglinide stimulate insulin secretion in a glucose-sensitive manner by inhibiting ATP-dependent potassium channels. As a result, there tends to be a lesser likelihood of hypoglycemia with repaglinide therapy compared to sulfonylureas.

Repaglinide is an antihyperglycemic agent, a meglitinide one. It is used in the treatment of non insulin dependent diabetes mellitus (NIDDM). This drug has the function to increase the insulin release by the pancreas to the blood. It does this by inhibiting the ATP-sensitive potassium channels in a glucose-dependent manner. This drug does not act on the insulin level without the presence of glucose, which differentiates it from sulfonylurea drugs. The mechanism of action starts with the need for functioning beta cells in the pancreas and glucose in the blood. Since the release of insulin is controlled by the beta cells membrane potential, the binding of repaglinide to the ATP-binding cassette subfamily C member 8 causes its immediate closing. This results in the depolarization of the beta cell and the opening of the L-type calcium channels. In consequence, the increased concentration of calcium results in the stimulation of the calcium-dependent exocytosis of insulin granules. An overdose of this drug may result in the development of hypoglycemic symptoms. Repaglinide is administered as an oral tablet.

Rescinnamine is an angiotensin-converting enzyme (ACE) inhibitor for the conversion of angiotensin I into angiotensin II. Angiotensin II is a critical circulating peptide hormone that has powerful vasoconstrictive effects and increases blood pressure. Rescinnamine is used to treat hypertension and high blood pressure as it decreases blood pressure. Rescinnamine is an alkaloid from Rauwolfia serpintina 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, Rescinnamine 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.

Benazepril, brand name Lotensin, 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. Benazepril is a prodrug which, following oral administration, undergoes biotransformation in vivo into its active form benazeprilat 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.