RISPERIDONE

Risperidone = Risperdal

Weight Average: 410.4845
Monoisotopic: 410.211804333
Chemical Formula:C23H27FN4O2
IUPAC Name:
3-[2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydropyrido[2,1-b]pyrimidin-4-one
CAS Registry No.106266-06-2
CHEBI:8871
ChEMBL Ligand: CHEMBL85
DrugBank Ligand:DB00734
DrugCentral Ligand: 2389
GtoPdb PubChem SID: 135650903
PubChem CID: 5073

Risperidone is a benzisoxazole derivative with antipsychotic property. 
Risperidone selectively antagonizes serotonin (5-HT) effects via cortical 5-HT2 receptor, and, to a lesser extent, competes with dopamine at the limbic dopamine D2 receptor. 
The antagonism leads to decreased psychotic effects, such as hallucinations and delusions. 
In addition, risperidone has low to moderate affinity for histamine H1, 5-HT1A, 5-HT1C, and 5-HT1D receptors, while Risperdal has weak affinity for dopamine D1 and haloperidol-sensitive sigma site receptors.
Risperidone is an atypical antipsychotic that is used widely in the treatment of mania and schizophrenia. 
Risperidone therapy is associated with serum aminotransferase elevations and in rare instances has been linked to clinically apparent acute liver injury.
Risperidone is a member of the class of pyridopyrimidines that is 2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one carrying an additional 2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl group at position 2. 
Risperdal has a role as a serotonergic antagonist, an alpha-adrenergic antagonist, a H1-receptor antagonist, a second generation antipsychotic, a dopaminergic antagonist, a psychotropic drug and an EC 3.4.21.26 (prolyl oligopeptidase) inhibitor. 
Risperdal is a pyridopyrimidine, an organofluorine compound, a heteroarylpiperidine and a member of 1,2-benzoxazoles.
Risperidone, a benzisoxazole derivative atypical antipsychotic medication, is proposed for inclusion in the WHO Model List of Essential Medications for treatment of schizophrenia, mania, and autism. 
To date, the list of essential medications does not include atypical antipsychotics, which play a critical role in the treatment of psychotic disorders. 
This application provides a systematic review of the use, efficacy, safety, availability, and cost-effectiveness of risperidone compared with both typical and other atypical antipsychotic medications.
Risperidone ISM® is a prolonged-release injectable antipsychotic developed and patented by ROVI for the treatment of schizophrenia in adults for whom the tolerability and effectiveness has been established with oral risperidone, since, as of the first injection, Ris perdalprovides immediate and sustained plasmatic drug levels and does not require loading doses or supplementation with oral risperidone.

What is risperidone?
Risperidone is an antipsychotic medicine that works by changing the effects of chemicals in the brain.
Risperidone is used to treat schizophrenia in adults and children who are at least 13 years old.
Risperidone is also used to treat symptoms of bipolar disorder (manic depression) in adults and children who are at least 10 years old.
Risperidone is also used to treat symptoms of irritability in autistic children who are 5 to 16 years old.
Risperdal is a medication known as an atypical antipsychotic that is used to treat symptoms of schizophrenia in teenagers and adults. 
Risperdal is also sometimes used to treat symptoms of bipolar disorder.

Definiton
An antipsychotic (neuroleptic) drug, derivative from benzisoxazole; also has sedative, antiemetic and hypothermic effect. 
Used in acute and chronic schizophrenia and others psychotic states with a predominance of productive and negative symptoms, affective disorders in various mental diseases, behavioral disorders in patients with dementia with the symptoms of aggression, disorders of activity or psychotic symptoms. 
Also prescribed as a mood stabilizer in the treatment of manias in bipolar disorders.

DESCRIPTION
RISPERDAL® contains risperidone, an atypical antipsychotic belonging to the chemical class of benzisoxazole derivatives. 
The chemical designation is 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one. 
Its molecular formula is C23H27FN4O2 and its molecular weight is 410.49. 

Risperidone Structural Formula Illustration
Risperidone is a white to slightly beige powder. 
Risperdal is practically insoluble in water, freely soluble in methylene chloride, and soluble in methanol and 0.1 N HCl.

Uses    
Antipsychotic Agents; Dopamine Antagonists; Serotonin Antagonists

MEDICATION
Human Drugs -> EU pediatric investigation plans
Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients
Pharmaceuticals
Risperidone is used to treat certain mental/mood disorders (such as schizophrenia, bipolar disorder, irritability associated with autistic disorder). 
Risperdal can help you to think clearly and take part in everyday life.Risperidone belongs to a class of drugs called atypical antipsychotics. 
Risperdal works by helping to restore the balance of certain natural substances in the brain.

Medical uses
Risperidone is mainly used for the treatment of schizophrenia, bipolar disorder, and irritability associated with autism.[10]

Schizophrenia
Risperidone is effective in treating psychogenic polydipsia and the acute exacerbations of schizophrenia.[11][12]
Studies evaluating the utility of risperidone by mouth for maintenance therapy have reached varying conclusions. 
A 2012 systematic review concluded that evidence is strong that risperidone is more effective than all first-generation antipsychotics other than haloperidol, but that evidence directly supporting its superiority to placebo is equivocal.
A 2011 review concluded that risperidone is more effective in relapse prevention than other first- and second-generation antipsychotics with the exception of olanzapine and clozapine.
A 2016 Cochrane review suggests that risperidone reduces the overall symptoms of schizophrenia, but firm conclusions are difficult to make due to very low-quality evidence. Data and information are scarce, poorly reported, and probably biased in favour of risperidone, with about half of the included trials developed by drug companies. 
The article raises concerns regarding the serious side effects of risperidone, such as parkinsonism.
A 2011 Cochrane review compared risperidone with other atypical antipsychotics such as olanzapine for schizophrenia.

Bipolar disorder
Second-generation antipsychotics, including risperidone, are effective in the treatment of manic symptoms in acute manic or mixed exacerbations of bipolar disorder.
In children and adolescents, risperidone may be more effective than lithium or divalproex, but has more metabolic side effects.
As maintenance therapy, long-acting injectable risperidone is effective for the prevention of manic episodes but not depressive episodes.
The long-acting injectable form of risperidone may be advantageous over long acting first generation antipsychotics, as it is better tolerated (fewer extrapyramidal effects) and because long acting injectable formulations of first generation antipsychotics may increase the risk of depression.[

Autism
Compared to placebo, risperidone treatment reduces certain problematic behaviors in autistic children, including aggression toward others, self-injury, challenging behaviour, and rapid mood changes.
The evidence for its efficacy appears to be greater than that for alternative pharmacological treatments.
Weight gain is an important adverse effect.
Some authors recommend limiting the use of risperidone and aripiprazole to those with the most challenging behavioral disturbances in order to minimize the risk of drug-induced adverse effects. 
Evidence for the efficacy of risperidone in autistic adolescents and young adults is less persuasive.

Other uses
Risperidone has shown promise in treating therapy-resistant obsessive–compulsive disorder, when serotonin reuptake inhibitors are not sufficient.
Risperidone has not demonstrated a benefit in the treatment of eating disorders or personality disorders.
While antipsychotic medications such as risperidone have a slight benefit in people with dementia, they have been linked to higher incidences of death and stroke. 
Because of this increased risk of death, treatment of dementia-related psychosis with risperidone is not FDA approved.

Methods of Manufacturing    
A Friedel-Crafts condensation of 1-acetylpiperidone-4-carbonyl chloride and 2,4-difluorobenzene, followed by hydrolysis of the N-acetyl group yields 4-(2,4-difluorobenzoyl)piperidone and the benzoyl carbonyl is converted to the oxime. 
With alkali, the fluorine atom in the 2-position is displaced through ring closure to form the isoxazole moiety. 
The secondary amine of the piperidine ring is alkylated with 3-(2-chloroethyl)pyridol[1,2-a]pyrimidin-4-one to yield the product.

Why it’s used
Risperidone is used to treat the symptoms of several psychiatric conditions. These include:

Schizophrenia. 
This is a mental health disorder that causes changes in thinking or perception. People with this condition may hallucinate (see or hear things that aren’t there) or have delusions (false beliefs about reality).
Acute manic or mixed episodes caused by bipolar I disorder. 
This drug may be given alone or with the drugs lithium or divalproex. 
People with bipolar disorder have intense mood episodes. These may include mania (an overly joyful or excited state), depression, or a mixture of both.
Irritability associated with autism. 
Autism affects how a person acts, interacts with others, learns, and communicates. 
Symptoms of irritability may include aggression toward others, thoughts of self-harm, strong expressions of frustration or anger, and mood shifts.

Computed Properties    
Molecular Weight:410.5    
XLogP3-AA:2.7    
Hydrogen Bond Donor Count: 0    
Hydrogen Bond Acceptor Count: 6    
Rotatable Bond Count: 4    
Exact Mass: 410.21180428    
Monoisotopic Mass:410.21180428    
Topological Polar Surface Area: 61.9 Ų    
Heavy Atom Count:30    
Formal Charge:0    
Complexity: 731    
Isotope Atom Count: 0    
Defined Atom Stereocenter Count:0    
Undefined Atom Stereocenter Count: 0    
Defined Bond Stereocenter Count: 0    
Undefined Bond Stereocenter Count: 0    
Covalently-Bonded Unit Count: 1    
Compound Is Canonicalized:Yes    

Visual appearance
Brick red coloured, round, biconvex, film coated tablets plain on both sides

General Mechanism of Action of Antipsychotic Drugs
Risperdal has been observed that from a pharmacodynamic perspective, all antipsychotics share a common feature: Risperdal reduce dopaminergic neurotransmission.  
According to the dopamine theory of schizophrenia, positive symptoms of schizophrenia might be explained through an overactivity of the mesolimbic pathway. 
Negative and cognitive symptoms of schizophrenia have been linked to a dysfunction of the mesocortical pathway . 

Drug and Medication Information    
Drug Indication    
Risperidone is indicated for the treatment of schizophrenia and irritability associated with autistic disorder. 
Risperdal is also indicated as monotherapy, or adjunctly with lithium or valproic acid, for the treatment of acute mania or mixed episodes associated with bipolar I disorder. 
Risperidone is additionally indicated in Canada for the short-term symptomatic management of aggression or psychotic symptoms in patients with severe dementia of the Alzheimer type unresponsive to nonpharmacological approaches. 
Risperidone is also used off-label for a number of conditions including as an adjunct to antidepressants in treatment-resistant depression.

Drug Warnings    
INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS. 
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Risperdal (risperidone) is not approved for the treatment of patients with dementia-related psychosis.
Like other antipsychotic agents (e.g., phenothiazines), risperidone has been associated with tardive dyskinesias. 
Although it has been suggested that atypical antipsychotics appear to have a lower risk of tardive dyskinesia, whether antipsychotic drugs differ in their potential to cause tardive dyskinesia is as yet unknown. 
In one open-label study, an annual incidence of tardive dyskinesia of 0.3% was reported in patients with schizophrenia who received approximately 8-9 mg of oral risperidone daily for at least 1 year. 
The prevalence of this syndrome appears to be highest among geriatric patients (particularly females). The risk of developing tardive dyskinesia and the likelihood that it will become irreversible also appear to increase with the duration of therapy and cumulative dose of antipsychotic agents administered.
However, the syndrome may occur, although much less frequently, after relatively short periods of treatment with low dosages.
Neuroleptic malignant syndrome (NMS), a potentially fatal symptom complex, has been reported in patients receiving antipsychotic agents. 
NMS requires immediate discontinuance of the drug and intensive symptomatic and supportive care.
Dose-related somnolence was a commonly reported adverse effect associated with risperidone treatment. 
Approximately 8% of adult patients with schizophrenia receiving 16 mg of oral risperidone daily and 1% of patients receiving placebo reported somnolence in studies utilizing direct questioning or a checklist to detect adverse events, respectively.

Pharmacology and Biochemistry    
Pharmacology    
The primary action of risperidone is to decrease dopaminergic and serotonergic pathway activity in the brain, therefore decreasing symptoms of schizophrenia and mood disorders. 
Risperidone has a high binding affinity for serotonergic 5-HT2A receptors when compared to dopaminergic D2 receptors in the brain. 
Risperidone binds to D2 receptors with a lower affinity than first-generation antipsychotic drugs, which bind with very high affinity. 
A reduction in extrapyramidal symptoms with risperidone, when compared to its predecessors, is likely a result of its moderate affinity for dopaminergic D2 receptors.

Pharmacological Classification    
Antipsychotic Agents
Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. 
Risperdal are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. 
These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. 
Many of these drugs may also be effective against nausea, emesis, and pruritus. 

Serotonin Antagonists
Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS. 

Dopamine Antagonists
Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. 
Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. 
Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. 
Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME. (See all compounds classified as Dopamine Antagonists.)

Absorption, Distribution and Excretion    
Absorption
Well absorbed. 
The absolute oral bioavailability of risperidone is 70% (CV=25%). 
The relative oral bioavailability of risperidone from a tablet is 94% (CV=10%) when compared to a solution.

Route of Elimination
Risperidone is extensively metabolized in the liver. 
In healthy elderly subjects, renal clearance of both risperidone and 9-hydroxyrisperidone was decreased, and elimination half-lives are prolonged compared to young healthy subjects.

Volume of Distribution
The volume of distribution of risperidone is approximately 1 to 2 L/kg.

Clearance
Risperidone is cleared by the kidneys. 
Clearance is decreased in the elderly and those with a creatinine clearance (ClCr) between 15-59 mL/min, in whom clearance is decreased by approximately 60%.
Risperidone is well absorbed. The absolute oral bioavailability of risperidone is 70% (CV=25%). 
The relative oral bioavailability of risperidone from a tablet is 94% (CV=10%) when compared to a solution.
Risperidone is rapidly distributed. The volume of distribution is 1-2 L/kg. 
In plasma, risperidone is bound to albumin and a1-acid glycoprotein. 
The plasma protein binding of risperidone is 90%, and that of its major metabolite, 9-hydroxyrisperidone, is 77%. 
Neither risperidone nor 9-hydroxyrisperidone displaces each other from plasma binding sites. High therapeutic concentrations of sulfamethazine (100 ug/mL), warfarin (10 ug/mL), and carbamazepine (10 ug/mL) caused only a slight increase in the free fraction of risperidone at 10 ng/mL and 9-hydroxyrisperidone at 50 ng/mL, changes of unknown clinical significance.
Plasma concentrations of risperidone, its major metabolite, 9-hydroxyrisperidone, and risperidone plus 9-hydroxyrisperidone are dose proportional over the dosing range of 1 to 16 mg daily (0.5 to 8 mg twice daily). 
Following oral administration of solution or tablet, mean peak plasma concentrations of risperidone occurred at about 1 hour. 
Peak concentrations of 9-hydroxyrisperidone occurred at about 3 hours in extensive metabolizers, and 17 hours in poor metabolizers. 
Steady-state concentrations of risperidone are reached in 1 day in extensive metabolizers and would be expected to reach steady-state in about 5 days in poor metabolizers. 
Steady-state concentrations of 9-hydroxyrisperidone are reached in 5-6 days (measured in extensive metabolizers).
Risperidone and 9-hydroxyrisperidone are present in human breast milk.

Metabolism/Metabolites    
Extensively metabolized by hepatic cytochrome P450 2D6 isozyme to 9-hydroxyrisperidone (i.e. [paliperidone]), which has approximately the same receptor binding affinity as risperidone. 
Hydroxylation is dependent on debrisoquine 4-hydroxylase and metabolism is sensitive to genetic polymorphisms in debrisoquine 4-hydroxylase. 
Risperidone also undergoes N-dealkylation to a lesser extent.
Risperidone is extensively metabolized in the liver. 
The main metabolic pathway is through hydroxylation of risperidone to 9-hydroxyrisperidone by the enzyme, CYP 2D6. 
A minor metabolic pathway is through N-dealkylation. The main metabolite, 9-hydroxyrisperidone, has similar pharmacological activity as risperidone. 
Consequently, the clinical effect of the drug results from the combined concentrations of risperidone plus 9-hydroxyrisperidone. CYP 2D6, also called debrisoquin hydroxylase, is the enzyme responsible for metabolism of many neuroleptics, antidepressants, antiarrhythmics, and other drugs. 
CYP 2D6 is subject to genetic polymorphism (about 6%-8% of Caucasians, and a very low percentage of Asians, have little or no activity and are "poor metabolizers") and to inhibition by a variety of substrates and some non-substrates, notably quinidine. 
Extensive CYP 2D6 metabolizers convert risperidone rapidly into 9-hydroxyrisperidone, whereas poor CYP 2D6 metabolizers convert it much more slowly. 
Although extensive metabolizers have lower risperidone and higher 9-hydroxyrisperidone concentrations than poor metabolizers, the pharmacokinetics of risperidone and 9-hydroxyrisperidone combined, after single and multiple doses, are similar in extensive and poor metabolizers.
Risperidone has known human metabolites that include:
3-[2-[4-(6-fluoro-2-hydroxy-1,2-benzoxazol-2-ium-3-yl)piperidin-1-yl]ethyl]-2,9-dimethyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one, 3-ethyl-2,9-dimethyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one, 6-Fluoro-3-(4-piperidinyl)-1,2-benzisoxazole, 9-Hydroxy-risperidone, and Paliperidone.

Biological Half-Life    
3 hours in extensive metabolizers Up to 20 hours in poor metabolizers
The apparent half-life of risperidone plus 9-hydroxyrisperidone following Risperdal Consta administration is 3 to 6 days, and is associated with a monoexponential decline in plasma concentrations. 
This half-life of 3-6 days is related to the erosion of the microspheres and subsequent absorption of risperidone.
The apparent half-life of risperidone was 3 hours (CV=30%) in extensive metabolizers and 20 hours (CV=40%) in poor metabolizers. 
The apparent half-life of 9-hydroxyrisperidone was about 21 hours (CV=20%) in extensive metabolizers and 30 hours (CV=25%) in poor metabolizers. 
The pharmacokinetics of risperidone and 9-hydroxyrisperidone combined, after single and multiple doses, were similar in extensive and poor metabolizers, with an overall mean elimination half-life of about 20 hours.

Background
Risperidone is a second-generation antipsychotic (SGA) medication used in the treatment of a number of mood and mental health conditions including schizophrenia and bipolar disorder.
Risperdal is one of the most widely used SGAs. 
Paliperidone, another commonly used SGA, is the primary active metabolite of risperidone (i.e. 9-hydroxyrisperidone).
Schizophrenia and various mood disorders are thought to be caused by an excess of dopaminergic D2 and serotonergic 5-HT2A activity, resulting in overactivity of central mesolimbic pathways and mesocortical pathways, respectively.
Risperidone is thought to reduce this overactivity through inhibition of dopaminergic D2 receptors and serotonergic 5-HT2A receptors in the brain.
Risperidone binds with a very high affinity to 5-HT2A receptors, approximately 10-20 fold greater than the drug's binding affinity to D2 receptors and carries lesser activity at several off-targets which may responsible for some of its undesirable effects.

Mechanism of Action    
Though Risperdal's 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 has high affinity for several receptors, including serotonin receptors (5-HT 2A/2C), D2 dopamine receptors and alpha1 and H1 receptors. 
Risperdal has no appreciable activity at M1 receptors. 

Risperdal's primary metabolite (9-hydroxyrisperidone) is nearly equipotent compared with the parent compound at D2 and 5-HT 2A receptors.
The exact mechanism of antipsychotic action of risperidone has not been fully elucidated but, like that of clozapine, appears to be more complex than that of most other antipsychotic agents and may involve antagonism of central type 2 serotonergic (5-HT2) receptors and central dopamine D2 receptors.
Risperidone is an atypical antipsychotic drug that is widely prescribed to young patients with different psychotic disorders. 
The long-term effects of this antipsychotic agent on neuronal receptors in developing brain remain unclear and require further investigation. 
In this study, we examined the effects of long-term treatment of risperidone on two serotonin receptor subtypes in brain regions of juvenile rat. Levels of 5-HT(1A) and 5-HT(2A) receptors in forebrain regions of juvenile rats were quantified after 3 weeks of treatment with three different doses of risperidone (0.3, 1.0 and 3.0mg/kg). 
Findings were compared to previously reported changes in 5-HT receptors after risperidone treatment (3.0mg/kg) in adult rat brain. The three doses of risperidone selectively and dose-dependently increased levels of 5-HT(1A) receptors in medial-prefrontal and dorsolateral-frontal cortices of juvenile animals. 
The higher doses (1.0 and 3.0mg/kg) of risperidone also increased 5-HT(1A) receptor binding in hippocampal CA(1) region of juvenile but not adult rats. 
In contrast, the three doses of risperidone significantly reduced 5-HT(2A) labeling in medial-prefrontal and dorsolateral-frontal cortices in juvenile as well as in adult animals in an equipotent fashion. 5-HT(1A) and 5-HT(2A) receptors in other forebrain regions were not altered by repeated risperidone treatment. 
These findings indicate that there are differential effects of risperidone on 5-HT(1A) and 5-HT(2A) receptors in juvenile animals, and that the 5-HT system in developing animals is more sensitive than adults to the long-term effects of risperidone.
The main class of atypical antipsychotic drugs (APDs) in current use includes the protypical atypical APD, clozapine, as well as aripiprazole, asenapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone. 
At clinically effective doses, these agents produce extensive blockade of serotonin (5-HT)(2A) receptors, direct or indirect stimulation of 5-HT(1A) receptors, and to a lesser extent, reduction in dopamine (DA) D(2) receptor-mediated neurotransmission. 
This contrasts with typical APDs, for example haloperidol and perphenazine, which are mainly DA D(2/)D(3) receptor antagonists and have weaker, if any, potency as 5-HT(2A) receptor antagonists. 
Some, but not all, atypical APDs are also effective 5-HT(2C) receptor inverse agonists or neutral antagonists, 5-HT(6) or 5-HT(7) receptor antagonists. 
This diverse action on 5-HT receptors may contribute to significant differences in efficacy and tolerability among the atypical APDs. 
There is considerable preclinical and some clinical evidence that effects on 5-HT receptors contribute to the low risk of producing extrapyramidal side effects, which is the defining characteristic of an atypical APD, the lack of elevation in plasma prolactin levels (with risperidone and 9-hydroxyrisperidone being exceptions), antipsychotic action, and ability to improve some domains of cognition in patients with schizophrenia. 
The serotonergic actions of the atypical APDs, especially 5-HT(2A) receptor antagonism, are particularly important to the differential effects of typical and atypical APDs to overcome the effects of acute or subchronic administration of N-methyl-d-aspartate (NMDA) receptor antagonists, such as phencyclidine, ketamine, and dizocipline (MK-801). 5-HT(1A) receptor stimulation and 5-HT(6) and 5-HT(7) receptor antagonism may contribute to beneficial effects of these agents on cognition. 
In particular, 5-HT(7) receptor antagonism may be the basis for the pro-cognitive effects of the atypical APD, amisulpride, a D(2)/D(3) receptor antagonist, which has no effect on other 5-HT receptor. 5-HT(2C) receptor antagonism appears to contribute to the weight gain produced by some atypical APDs and may also affect cognition and psychosis via its influence on cortical and limbic dopaminergic activity.
Paliperidone is an active metabolite of the second-generation atypical antipsychotic, risperidone recently approved for the treatment of schizophrenia and schizoaffective disorder. 
Because paliperidone differs from risperidone by only a single hydroxyl group, questions have been raised as to whether there are significant differences in the effects elicited between these two drugs. 
/The researchers/ compared the relative efficacies of paliperidone versus risperidone to regulate several cellular signalling pathways coupled to four selected GPCR targets that are important for either therapeutic or adverse effects: human dopamine D2 , human serotonin 2A receptor subtype (5-HT2A ), human serotonin 2C receptor subtype and human histamine H1 receptors. 
Whereas the relative efficacies of paliperidone and risperidone were the same for some responses, significant differences were found for several receptor-signalling systems, with paliperidone having greater or less relative efficacy than risperidone depending upon the receptor-response pair. 
Interestingly, for 5-HT2A -mediated recruitment of beta-arrestin, 5-HT2A -mediated sensitization of ERK, and dopamine D2 -mediated sensitization of adenylyl cyclase signalling, both paliperidone and risperidone behaved as agonists. 
These results suggest that the single hydroxyl group of paliperidone promotes receptor conformations that can differ from those of risperidone leading to differences in the spectrum of regulation of cellular signal transduction cascades. 
Such differences in signalling at the cellular level could lead to differences between paliperidone and risperidone in therapeutic efficacy or in the generation of adverse effects.

Key facts
Risperidone works by affecting chemical messengers in the brain (neurotransmitters) like dopamine. 
Risperdal does not cure your condition but Risperdal helps to keep your symptoms under control.
Risperidone does not work straight away. 
Risperdal can take several days or even months for some symptoms to get better.
Common side effects include feeling sleepy, problems with your movement and headaches.
It can make you feel more hungry than usual, so you may put on weight.
It's best not to drink alcohol for the first few days of treatment until you see how the medicine affects you.

Risperidone side effects
Risperidone oral tablet may cause drowsiness and the feeling of being unstable. 
This may lead to falling, which can cause broken bones or other health problems.

You may be at a higher risk for falls if you’re an adult who’s over age 65 years and taking other medications that cause drowsiness.

More common side effects
The more common side effects of risperidone can include:
parkinsonism (trouble moving)
akathisia (restlessness and urge to move)
dystonia (muscle contractions that cause twisting and repetitive movements that you can’t control)
tremors (uncontrollable rhythmic movement in one part of your body)
sleepiness and fatigue
dizziness
anxiety
blurred vision
abdominal pain or discomfort
drooling
dry mouth
increased appetite or weight gain
rash
stuffy nose 
upper respiratory tract infections
inflammation of your nose and throat

Why has risperidone been prescribed?
Risperidone is an antipsychotic used to treat schizophrenia and other similar conditions.

What are the benefits of taking risperidone?
Antipsychotics are effective in reducing the symptoms of psychosis. 
They also shorten the time to recovery and help prevent relapses.

Alternative Names
risperidone
106266-06-2
Risperidal
Risperdal
Rispolept
Risperdal Consta
Risperin
Rispolin
Sequinan
Apexidone
Risperidonum
Risperidona
Risperdal M-Tab
Belivon
Psychodal
Spiron
R 64 766
C23H27FN4O2
UNII-L6UH7ZF8HC
R 64766
R 64,766
R-64766
3-[2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one
CHEMBL85
MFCD00274576
L6UH7ZF8HC
3-(2-(4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)ethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one
3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one
Risperidal M-Tab
CHEBI:8871
Risperidonum [Latin]
Risperidona [Spanish]
R-64-766
106266-06-2 (free base)
Risperidone, 99%
3-{2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl}-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one
NCGC00015883-05
CAS-106266-06-2
DSSTox_CID_25193
DSSTox_RID_80740
DSSTox_GSID_45193
3-{2-[4-(6-FLUORO-BENZO[D]ISOXAZOL-3-YL)-PIPERIDIN-1-YL]-ETHYL}-2-METHYL-6,7,8,9-TETRAHYDRO-PYRIDO[1,2-A]PYRIMIDIN-4-ONE
Zophrenal
Risperdal (TN)
3-[2-[4-(6-fluoranyl-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one