Pathways

Fluvastatin inhibits cholesterol synthesis via the mevalonate pathway by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase is the enzyme responsible for the conversion of HMG-CoA to mevalonic acid, the rate-limiting step of cholesterol synthesis by this pathway. Fluvastatin bears a chemical resemblance to the reduced HMG-CoA reaction intermediate that is formed during catalysis. Fluvastatin was the first synthetically-prepared HMG-CoA reductase inhibitor. Although similar to lovastatin, simvastatin, and pravastatin, it has a shorter half-life, no active metabolites, extensive protein binding, and minimal CSF penetration. Cholesterol biosynthesis accounts for approximately 80% of cholesterol in the body; thus, inhibiting this process can significantly lower cholesterol levels.

Statins are a class of medications that lower lipid levels and are administered to reduce illness and mortality in people who are at high risk of cardiovascular disease. Fluvastatin is a well-tolerated orally-administered synthetic statin that reduces total cholesterol levels, low-density lipoprotein (LDL)-cholesterol, triglyceride, and very-low-density lipoprotein (VLDL)-cholesterol. It also increases levels of high-density lipoprotein (HDL)-cholesterol. It reduces cholesterol biosynthesis as a result of a prolonged duration of HMG-CoA reductase inhibition. Reported side effects of fluvastatin include gastrointestinal upset (diarrhea, nausea, constipation, gas, abdominal pain), myotoxicity (myopathy, myositis, rhabdomyolysis), and hepatotoxicity. The primary therapeutic mechanism of action of statins is the inhibition of the rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase in hepatocytes. HMG-CoA reductase catalyzes the conversion of HMG-CoA into mevalonic acid, a precursor for cholesterol biosynthesis. Statins bind reversibly to the active site of HMG-CoA reductase and the subsequent structural change in the enzyme effectively disables it. Due to the resulting decrease in intracellular sterol levels, the ER membrane protein INSIG no longer binds to SREBP cleavage-activating protein (SCAP) which is, itself, bound to the transcription factor sterol regulatory element-binding protein (SREBP). Freed from INSIG, SCAP escorts SREBP to the Golgi apparatus from the ER as cargo in COPII vesicles. At the Golgi membrane, two proteases, S1P and S2P, sequentially cleave the SCAP-SREBP complex, releasing the mature form of SREBP into the cytoplasm. SREBP then translocates to the nucleus where it is transported into the nucleoplasm by binding directly to importin beta in the absence of importin alpha. SREBP binds to the sterol regulatory element (SRE) present in the promoter region of genes involved in cholesterol uptake and cholesterol synthesis, including the gene encoding the low-density lipoprotein (LDL) receptor (LDL-R). As a result, LDL-R gene transcription increases which then leads to an increased synthesis of the LDL-R protein. LDL-R localizes to the endoplasmic reticulum for transport and exocytosis to the cell surface. The elevated amount of LDL-R results in more circulating free LDL cholesterol binding and subsequent internalization via endocytosis. Lysosomal degradation of the internalized LDL cholesterol elevates cellular cholesterol levels to maintain homeostasis. This drug is administered as an oral tablet.

Fluvoxamine, an aralkylketone-derivative agent, is one of a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs) that differs structurally from other SSRIs. It is used to treat the depression associated with mood disorders. It is also used on occasion in the treatment of body dysmorphic disorder and anxiety. The antidepressant, antiobsessive-compulsive, and antibulimic actions of fluvoxamine are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. It's mechanism of action it to bind selectively bind to the sodium dependent serotonin transporter and blocking the recycling of serotonin from the synapse. As serotonin accumulates it enhances the serotonergic function of the 5-hydroxytryptamine 1A receptor leading to decreased anxiety and depressive moods.

Fluvoxamine, an aralkylketone-derivative agent, is one of a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs) that differs structurally from other SSRIs. It is used to treat the depression associated with mood disorders. It is also used on occasion in the treatment of body dysmorphic disorder and anxiety. The antidepressant, antiobsessive-compulsive, and antibulimic actions of fluvoxamine are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. It's mechanism of action it to bind selectively bind to the sodium dependent serotonin transporter and blocking the recycling of serotonin from the synapse. As with other SSRIs, it showed weak effects on norepinephrine and dopamine neuronal reuptake. As serotonin accumulates it enhances the serotonergic function of the 5-hydroxytryptamine 1A receptor leading to decreased anxiety and depressive moods.

Fluvoxamine, an aralkylketone-derivative agent, is one of a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs) that differs structurally from other SSRIs. It is used to treat the depression associated with mood disorders. It is also used on occasion in the treatment of body dysmorphic disorder and anxiety. The antidepressant, antiobsessive-compulsive, and antibulimic actions of fluvoxamine are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. It's mechanism of action it to bind selectively bind to the sodium dependent serotonin transporter and blocking the recycling of serotonin from the synapse. As with other SSRIs, it showed weak effects on norepinephrine and dopamine neuronal reuptake. As serotonin accumulates it enhances the serotonergic function of the 5-hydroxytryptamine 1A receptor leading to decreased anxiety and depressive moods.

Metabolites of Fluvoxamine are predicted with biotransformer.

The biosynthesis of folic acid begins with a product of purine nucleotides de novo biosynthesis pathway, GTP. This compound is involved in a reaction with water through a GTP cyclohydrolase 1 protein complex, resulting in a hydrogen ion, formic acid and 7,8-dihydroneopterin 3-triphosphate. The latter compound is dephosphatased through a dihydroneopterin triphosphate pyrophosphohydrolase resulting in the release of a pyrophosphate, hydrogen ion and 7,8-dihydroneopterin 3-phosphate. The latter compound reacts with water spontaneously resulting in the release of a phosphate and a 7,8 -dihydroneopterin. This compound reacts with a dihydroneopterin aldolase, releasing a glycoaldehyde and 6-hydroxymethyl-7,9-dihydropterin. The latter compound is phosphorylated with a ATP-driven 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase resulting in a (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate. Chorismate is metabolized by reacting with L-glutamine through a 4-amino-4-deoxychorismate synthase resulting in L-glutamic acid and 4-amino-4-deoxychorismate. The latter compound then reacts through an aminodeoxychorismate lyase resulting in pyruvic acid,hydrogen ion and p-aminobenzoic acid. (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate and p-aminobenzoic acid react through a dihydropteroate synthase resulting in pyrophosphate and 7,8-dihydropteroic acid. This compound reacts with L-glutamic acid through an ATP driven bifunctional folylpolyglutamate synthetase / dihydrofolate synthetase resulting in a 7,8-dihydrofolate monoglutamate. This compound is reduced through an NADPH mediated dihydrofolate reductase resulting in a tetrahydrofate. This product goes on to a one carbon pool by folate pathway.

The biosynthesis of folic acid begins as a product of purine nucleotides de novo biosynthesis pathway. Purine nucleotides are involved in a reaction with water through a GTP cyclohydrolase 1 protein complex, resulting in a hydrogen ion, formic acid and 7,8-dihydroneopterin 3-triphosphate. The latter compound is dephosphorylated through a dihydroneopterin triphosphate pyrophosphohydrolase resulting in the release of a pyrophosphate, hydrogen ion and 7,8-dihydroneopterin 3-phosphate. The latter product reacts with water spontaneously resulting in the release of a phosphate and a 7,8 -dihydroneopterin. 7,8 -dihydroneopterin reacts with a dihydroneopterin aldolase, releasing a glycoaldehyde and 6-hydroxymethyl-7,9-dihydropterin. Continuing, 6-hydroxymethyl-7,9-dihydropterin is phosphorylated with a ATP-driven 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase resulting in a (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate. Chorismate is metabolized by reacting with L-glutamine through a 4-amino-4-deoxychorismate synthase resulting in L-glutamic acid and 4-amino-4-deoxychorismate. The latter product is then catalyzed via an aminodeoxychorismate lyase resulting in pyruvic acid, hydrogen ion and p-aminobenzoic acid. (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate and p-aminobenzoic acid react with the help of a dihydropteroate synthase resulting in pyrophosphate and 7,8-dihydropteroic acid. This compound then reacts with L-glutamic acid through an ATP driven bifunctional folylpolyglutamate synthease / dihydrofolate synthease resulting in a 7,8-dihydrofolate monoglutamate. 7,8-dihydrofolate monoglutamate is then reduced via a NADPH mediated dihydrofolate reductase resulting in a tetrahydrofate which will continue and become a metabolite of the folate pathway