Pathways

Risedronic acid is indicated for the treatment of osteoperosis in men, treatment of Paget's disease, treatment and prevention of osteoperosis in postmenopausal women, and treatment and prevention of glucocorticoid-induced osteoperosisLabel. Risedronatic acid binds to bone hydroxyapatiteLabel. Bone resorption causes local acidification, releasing risedronic acid which is that taken into osteoclasts by fluid-phase endocytosis1. Endocytic vesicles are acidified, releasing risedronic acid to the cytosol of osteoclasts where they induce apoptosis through inhbition of farnesyl pyrophosphate synthase1. Inhibition of osteoclasts results in decreased bone resorption1.

Risedronate (also named Actonel, Atelvia or Benet.) is a type of medication that used to treat numbers of bone diseases because of its affinity for hydroxyapatite. Risedronate 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).

Risedronate also known as risedronic acid, is a third-generation bisphosphonate used to treat osteoporosis and Paget's disease. Risedronate binds to hydroxyapatite, during bone resorption risedronate is released and taken up by osteoclast through endocytosis. It goes to inhibit farnesyl pyrophosphate synthase, by doing so the components needed for prenylation lead to apoptosis within the osteoclast. In order to maximize absorption after consuming orally, it is best to avoid eating prior to consumption. Some patients may require supplements such as vitamin D and avoid calcium, antacids and divalent ions as it interferes with absorption.

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.

Risperidone is a second-generation antipsychotic medication used to treat a number of mental health disorders including schizophrenia, bipolar mania, psychosis, or as an adjunct in severe depression. Though its precise mechanism of action is not fully understood, current focus is on the ability of risperidone to inhibit the D2 dopaminergic receptors and 5-HT2A serotonergic receptors in the brain. Schizophrenia is thought to result from an excess of dopaminergic D2 and serotonergic 5-HT2A activity, resulting in overactivity of central mesolimbic pathways and mesocortical pathways, respectively. D2 dopaminergic receptors are transiently inhibited by risperidone, reducing dopaminergic neurotransmission, therefore decreasing positive symptoms of schizophrenia, such as delusions and hallucinations. Risperidone binds transiently and with loose affinity to the dopaminergic D2 receptor, with an ideal receptor occupancy of 60-70% for optimal effect. Rapid dissociation of risperidone from the D2 receptors contributes to decreased risk of extrapyramidal symptoms (EPS), which occur with permanent and high occupancy blockade of D2 dopaminergic receptors. Low-affinity binding and rapid dissociation from the D2 receptor distinguish risperidone from the traditional antipsychotic drugs. A higher occupancy rate of D2 receptors is said to increase the risk of extrapyramidal symptoms and is therefore to be avoided. Increased serotonergic mesocortical activity in schizophrenia results in negative symptoms, such as depression and decreased motivation. The high-affinity binding of risperidone to 5-HT2A receptors leads to a decrease in serotonergic activity. In addition, 5-HT2A receptor blockade results in decreased risk of extrapyramidal symptoms, likely by increasing dopamine release from the frontal cortex, and not the nigrostriatal tract. Dopamine level is therefore not completely inhibited. Through the above mechanisms, both serotonergic and D2 blockade by risperidone are thought to synergistically work to decrease the risk of extrapyramidal symptoms. Risperidone has also been said to be an antagonist of alpha-1 (α1), alpha-2 (α2), and histamine (H1) receptors. Blockade of these receptors is thought to improve symptoms of schizophrenia, however the exact mechanism of action on these receptors is not fully understood at this time.

Risperidone is a second-generation antipsychotic medication used to treat a number of mental health disorders including schizophrenia, bipolar mania, psychosis, or as an adjunct in severe depression. Paliperidone is the primary active metabolite of risperidone. The two antipsychotics are also metabolized differently, as risperidone is metabolized in the liver mainly by the polymorphic cytochrome P450 2D6 (CYP2D6) to its active metabolite 9-hydroxyrisperidone (paliperidone). Paliperidone, by contrast, is predominantly excreted unchanged in the urine. The main route of risperidone metabolism is in the liver by the enzyme CYP2D6. The major active metabolite, 9-hydroxyrisperidone, contributes to the pharmacological effects of this drug. While risperidone and 9-hydroxyrisperidone are often regarded as equipotent, they display different affinities towards the two target receptors (D2 and 5HT2A), where risperidone appears to be approximately 2-fold more potent than 9-hydroxyrisperidone. There is also a difference in brain distribution; risperidone is distributed more to the CNS. Though its precise mechanism of action is not fully understood, current focus is on the ability of risperidone to inhibit the D2 dopaminergic receptors and 5-HT2A serotonergic receptors in the brain. Schizophrenia is thought to result from an excess of dopaminergic D2 and serotonergic 5-HT2A activity, resulting in overactivity of central mesolimbic pathways and mesocortical pathways, respectively. D2 dopaminergic receptors are transiently inhibited by risperidone, reducing dopaminergic neurotransmission, therefore decreasing positive symptoms of schizophrenia, such as delusions and hallucinations. Risperidone binds transiently and with loose affinity to the dopaminergic D2 receptor, with an ideal receptor occupancy of 60-70% for optimal effect. Rapid dissociation of risperidone from the D2 receptors contributes to decreased risk of extrapyramidal symptoms (EPS), which occur with permanent and high occupancy blockade of D2 dopaminergic receptors. Low-affinity binding and rapid dissociation from the D2 receptor distinguish risperidone from the traditional antipsychotic drugs. A higher occupancy rate of D2 receptors is said to increase the risk of extrapyramidal symptoms and is therefore to be avoided. Increased serotonergic mesocortical activity in schizophrenia results in negative symptoms, such as depression and decreased motivation. The high-affinity binding of risperidone to 5-HT2A receptors leads to a decrease in serotonergic activity. In addition, 5-HT2A receptor blockade results in decreased risk of extrapyramidal symptoms, likely by increasing dopamine release from the frontal cortex, and not the nigrostriatal tract. Dopamine level is therefore not completely inhibited. Through the above mechanisms, both serotonergic and D2 blockade by risperidone are thought to synergistically work to decrease the risk of extrapyramidal symptoms. Risperidone has also been said to be an antagonist of alpha-1 (α1), alpha-2 (α2), and histamine (H1) receptors. Blockade of these receptors is thought to improve symptoms of schizophrenia, however the exact mechanism of action on these receptors is not fully understood at this time.

Risperidone is a second-generation antipsychotic medication used to treat a number of mental health disorders including schizophrenia, bipolar mania, psychosis, or as an adjunct in severe depression. Paliperidone is the primary active metabolite of risperidone. The two antipsychotics are also metabolized differently, as risperidone is metabolized in the liver mainly by the polymorphic cytochrome P450 2D6 (CYP2D6) to its active metabolite 9-hydroxyrisperidone (paliperidone). Paliperidone, by contrast, is predominantly excreted unchanged in the urine. The major active metabolite, 9-hydroxyrisperidone, contributes to the pharmacological effects of this drug. While risperidone and 9-hydroxyrisperidone are often regarded as equipotent, they display different affinities towards the two target receptors (D2 and 5HT2A), where risperidone appears to be approximately 2-fold more potent than 9-hydroxyrisperidone. There is also a difference in brain distribution; risperidone is distributed more to the CNS. Though its precise mechanism of action is not fully understood, current focus is on the ability of risperidone to inhibit the D2 dopaminergic receptors and 5-HT2A serotonergic receptors in the brain. Schizophrenia is thought to result from an excess of dopaminergic D2 and serotonergic 5-HT2A activity, resulting in overactivity of central mesolimbic pathways and mesocortical pathways, respectively. D2 dopaminergic receptors are transiently inhibited by risperidone, reducing dopaminergic neurotransmission, therefore decreasing positive symptoms of schizophrenia, such as delusions and hallucinations. Risperidone binds transiently and with loose affinity to the dopaminergic D2 receptor, with an ideal receptor occupancy of 60-70% for optimal effect. Rapid dissociation of risperidone from the D2 receptors contributes to decreased risk of extrapyramidal symptoms (EPS), which occur with permanent and high occupancy blockade of D2 dopaminergic receptors. Low-affinity binding and rapid dissociation from the D2 receptor distinguish risperidone from the traditional antipsychotic drugs. A higher occupancy rate of D2 receptors is said to increase the risk of extrapyramidal symptoms and is therefore to be avoided. Increased serotonergic mesocortical activity in schizophrenia results in negative symptoms, such as depression and decreased motivation. The high-affinity binding of risperidone to 5-HT2A receptors leads to a decrease in serotonergic activity. In addition, 5-HT2A receptor blockade results in decreased risk of extrapyramidal symptoms, likely by increasing dopamine release from the frontal cortex, and not the nigrostriatal tract. Dopamine level is therefore not completely inhibited. Through the above mechanisms, both serotonergic and D2 blockade by risperidone are thought to synergistically work to decrease the risk of extrapyramidal symptoms. Risperidone has also been said to be an antagonist of alpha-1 (α1), alpha-2 (α2), and histamine (H1) receptors. Blockade of these receptors is thought to improve symptoms of schizophrenia, however the exact mechanism of action on these receptors is not fully understood at this time.

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