Pathways

Metabolites of Ziprasidone are predicted with biotransformer.

Ziprasidone is an atypical antipsychotic used to treat schizophrenia, bipolar mania, and acute agitation in schizophrenic patients. It also indicated improvement on the manic syndrome subscale that measures symptoms of mania such as mood, insomnia, excessive energy and activity, and overall behavior and ideation. Ziprasidone is also used as off-labeled for monotherapy in acute hypomania, monotherapy as maintenance treatment for adult patients with bipolar I disorder, hyperactivity treatment, and for the treatment of delirium in the ICU. Ziprasidone presents in both oral capsule and intramuscular injection formulations. Ziprasidone is an atypical antipsychotic that has a binding affinity for dopaminergic (DA), serotonergic (5HT), adrenergic (a1), and histaminergic (HA) receptors. Regarding treatment for schizophrenia, antagonism of the dopamine (D2) receptor in the mesolimbic pathway has proven efficacious in diminishing positive symptoms, whereas the antagonism of the 5HT2A receptor in the mesocortical pathway has demonstrated reduction of negative symptoms of psychosis. Its efficacy and mechanism of action for treating bipolar disorder are unknown. The antagonization of both histaminergic and adrenergic (a1) receptors can induce somnolence and orthostatic hypotension.

Zofenopril is a specific angiotensin-converting enzyme (ACE) inhibitor. It is used in the treatment of acute myocardial infaction (AMI), hypertension and mild to mmoderate hypertension. Zafenopril has the ability to improve endothelial function and protect against ischemia. Zofenopril is a prodrug, once absorbed, the cell metabolizes it in zofenoprilat. Zefonoprilat is the molecule that does the inhibition of the ACEs. This interaction blocks the conversion of angiotensin I to angiotensin II. This production of angiotensin II modulates blood pressure. Angiotensin II causes vasoconstriction and this leads to an increase of blood pressure. This system starts with the renin being released from prorenin due to kallikrein. After that, renin will cleave angiotensinogen to release angiotensin I. Angiotensin II binds to AT1 and AT2, these receptors will activate many signaling cascades that will lead to the retaining of sodium and water in the renal tubules. At the same time, these receptors will activate signaling cascades that lead to the stimulation of aldosterone release from the adrenal gland (an important role in the renin-angiotensin-aldosterone system (RAAS)).

Zoledronic acid, or CGP 42'446,8 is a third generation, nitrogen containing bisphosphonate similar to ibandronic acid, minodronic acid, and risedronic acid. Zoledronic acid is used to treat and prevent multiple forms of osteoporosis, hypercalcemia of malignancy, multiple myeloma, bone metastases from solid tumors, and Paget’s disease of bone.Zoledronic acid was first described in the literature in 1994. Zoledronic acid is indicated to treat hypercalcemia of malignancy, multiple myeloma, bone metastases from solid tumors, osteoporosis in men and postmenopausal women, glucocorticoid induced osteoporosis, and Paget's disease of bone in men and women.Zoledronic acid is also indicated for the prevention of osteoporosis in post menopausal women and glucocorticoid induced osteoporosis Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis. Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act. Osteoclasts mediate resorption of bone. When osteoclasts bind to bone they form podosomes, ring structures of F-actin. Etidronic acid also inhibits V-ATPases in the osteoclast, though the exact subunits are unknown, preventing F-actin from forming podosomes. Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption. Nitrogen containing bisphosphonates such as zoledronate are known to induce apoptosis of hematopoietic tumor cells by inhibiting the components of the mevalonate pathway farnesyl diphosphate synthase, farnesyl diphosphate, and geranylgeranyl diphosphate. These components are essential for post-translational prenylation of GTP-binding proteins like Rap1. The lack of prenylation of these proteins interferes with their function, and in the case of Rap1, leads to apoptosis. zoledronate also activated caspases which further contribute to apoptosis.

Zoledronate (also named zoledronic acid, Zometa or Reclast) is a type of medication that used to treat numbers of bone diseases because of its affinity for hydroxyapatite. Zoledronate targets farnesyl pyrophosphate (FPP) synthase by inhibiting the function of this enzyme in the mevalonate pathway, which prevent the biosynthesis of Geranyl-PP and farnesyl pyrophosphate. Geranyl-PP and farnesyl pyrophosphate are important for geranylgeranylation and farnesylation of GTPase signalling proteins. Lack of Geranyl-PP and farnesyl pyrophosphate will result in decreased rate of bond resorption and turnover as well as block the osteoclast activity, which lead to an increasing mass gain in bone (i.e. net gain in bone mass).

Zoledronate also known as zoledronic acid is a third-generation bisphosphonate used to treat malignancy with hypercalcemia, myeloma and bone metastasis from tumors. Zoledronate is taken up into the bone and binds to hydroxyapatite, during bone resorption zoledronate is released and taken up into the osteoclast by endocytosis. Within the cytosol of the osteoclast, it inhibits geranylgeranyl pyrophosphate synthase and farnesyl pyrophosphate synthase. Without these enzymes components needed for the prenylation of proteins are stopped, and this leads to apoptosis of the osteoclast.

Zoledronate D,L-Lysine Monohydrate is a drug that is not metabolized by the human body as determined by current research and biotransformer analysis. Zoledronate D,L-Lysine Monohydrate passes through the liver and is then excreted from the body mainly through the kidney.

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