Pathways

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.

Zolmitriptan, like other triptans, is a serotonin (5-hydroxytryptamine; 5-HT) receptor agonist, with enhanced specificity for the 5-HT1B and 5-HT1D receptor subtypes. It is through the downstream effects of 5-HT1B/1D activation that triptans are proposed to provide acute relief of migraines. It has a weak affinity for 5-HT 1A receptor. Zolmitriptan is a vasoconstrictor, leading to possible adverse cardiovascular effects such as myocardial ischemia/infarction, arrhythmias, cerebral and subarachnoid hemorrhage, stroke, gastrointestinal ischemia, and peripheral vasospastic reactions.

Zolpidem is a sedative hypnotic used for the short-term treatment of insomnia to improve sleep latency. Zolpidem binds on the benzodiazepine receptors in the post-synaptic GABA-A ligand-gated chloride channel in different sites of the central nervous system (CNS). This binding will result in an increase on the GABA inhibitory effects which is translated as an increase in the flow of chloride ions into the cell causing hyperpolarization and stabilization of the cellular plasma membrane. Zolpidem binding to the GABAA receptor chloride channel macromolecular complex is thought to lead to the sedative, anticonvulsant, anxiolytic, and myorelaxant drug effects of the drug.