Pathways

Metabolites of Atosiban are predicted with biotransformer.

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. Atorvastatin (trade name: Lipitor) is a well-tolerated orally-administered synthetic statin that reduces levels of total cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, and very-low-density lipoprotein (VLDL)-cholesterol. It also increases levels of high-density lipoprotein (HDL)-cholesterol. Atorvastatin's efficacy is greater than other statins in reducing total cholesterol and LDL-cholesterol levels. This is theorized to be the result of a prolonged duration of HMG-CoA reductase inhibition. Reported side effects of atorvastatin include constipation, flatulence, dyspepsia (indigestion), abdominal pain, headache, and myalgia (muscle pain). 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.

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. Atorvastatin (trade name: Lipitor) is a well-tolerated orally-administered synthetic statin that reduces levels of total cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, and very-low-density lipoprotein (VLDL)-cholesterol. It also increases levels of high-density lipoprotein (HDL)-cholesterol. Atorvastatin's efficacy is greater than other statins in reducing total cholesterol and LDL-cholesterol levels. This is theorized to be the result of a prolonged duration of HMG-CoA reductase inhibition. Reported side effects of atorvastatin include constipation, flatulence, dyspepsia (indigestion), abdominal pain, headache, and myalgia (muscle pain). 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 actively 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 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 the binding of more circulating free LDL cholesterol and subsequent internalization via endocytosis. Lysosomal degradation of the internalized LDL cholesterol elevates cellular cholesterol levels to maintain homeostasis.

Atomoxetine, also known as Strattera, is a selective norepinephrine reuptake inhibitor (SNRI). It is used in the management of attention deficit hyperactivity disorder (ADHD). Although the underlying pathophysiology that causes ADHD remains undefined, evidence suggests that dysregulation in noradrenergic and dopaminergic pathways plays a critical role. Due to atomoxetine's noradrenergic activity, it also has effects on the cardiovascular system such as increased blood pressure and tachycardia. Atomoxetine binds to the sodium-dependent noradrenaline transporter, this prevents the noradrenaline reuptake in the presynaptic neurons. In consequence, there is more norepinephrine available in the synapses and in the brain in general. This will increase the activation of alpha-adrenergic receptors in the postsynaptic neurons. This activation decreases the inattention of ADHD patients. This drug is administered as an oral capsule.

Atomoxetine classified as a selective norepinephrine reuptake inhibitor (SNRI) commonly used in the treatment of attention deficit hyperactivity disorder (ADHD) instead of stimulant medication such as methylphenidate, dextroamphetamine or lisdexamfetamine. Atomoxetine appears to only increase norepinephrine and dopamine levels within the prefrontal cortex without effecting concentration levels in the nucleus accumbens and or the striatum leading to little to no stimulant associated side effects with less abuse potential. It is a selective reuptake inhibitor of norepinephrine transporter (NET) leading to alleviating symptoms of ADHD. Recent studies have also shown that its binds to serotonin transporter (SERT) and also inhibits N-methyl-d-aspartate (NMDA) receptors, although further research is necessary to confirm these interactions. It is metabolized by cytochrome P450 2D6 into its metabolites of 4-hydroxy-atomoxetine which is equipotent as atomoxetine and its mechanism of action. If there is a lack of CYP2D6 enzymes then other cytochrome enzymes break down the drug and results in its minor metabolites being formed with less pharmacological activity. The metabolites are commonly glucuronidated and excreted as 4-hydroxyatomoxetine-O-glucuronide through the urine. During acute or chronic overdoses of atomoxetine, some symptoms observed is gastrointestinal symptoms, somnolence, dizziness, tremor and abnormal behavior. If these symptoms are seen poison control center should be phoned in order to plan a good course of action, as atomoxetine is protein bound and dialysis may not be effective treatment for an overdose.

Metabolites of Atogepant are predicted with biotransformer.