Risperidone Stats & Data
Fc1ccc2c(c1)onc2C1CCN(CC1)CCc1c(C)nc2CCCCn2c1=ORAPZEAPATHNIPO-UHFFFAOYSA-NPharmacology
DrugBankDescription
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. It 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 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.
Pharmacodynamics
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.
Metabolism
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.
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.
Indication
Risperidone is indicated for the treatment of schizophrenia and irritability associated with autistic disorder. It 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.
Half-life
3 hours in extensive metabolizers Up to 20 hours in poor metabolizers
Protein Binding
Risperidone and its active metabolite, 9-hydroxyrisperidone, are ~88% and ~77% protein-bound in human plasma, respectively. They each bind to both serum albumin and alpha-1-acid glycoprotein.
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%.
Measured Affinities
Guide to PHARMACOLOGYMeasured binding and functional data for risperidone, curated by the IUPHAR/BPS Guide to PHARMACOLOGY. Each row cites the paper it came from. Lower concentrations mean tighter binding — a value in the sub-nanomolar range indicates a very potent interaction.
| Target | Action | Measure | Value | Concentration | Species | Source |
|---|---|---|---|---|---|---|
| D2 receptor DRD2 | Antagonist | pKi | 9.36 | 0.437 nM | Human | PMID 9430133 |
| 5-HT2A receptor Htr2a | Antagonist | pKi | 8.5 | 3.16 nM | Rat | PMID 9655845 |
| α1D-adrenoceptor ADRA1D | Antagonist | pKi | 7.4 | 39.81 nM | Human | PMID 11459121 |
| α2A-adrenoceptor ADRA2A | Antagonist | pKi | 7.3 | 50.12 nM | Human | PMID 35224877 |
| D3 receptor DRD3 | Antagonist | pKi | 7 | 100 nM | Human | PMID 7473180 |
| 5-HT1A receptor Htr1a | Antagonist | pKi | 6.2 | 630.96 nM | Rat | PMID 8997630 |
| 5-HT1F receptor HTR1F | Antagonist | pKi | 5.9 | 1,259 nM | Human | PMID 8935801 |
| 5-ht1e receptor HTR1E | Antagonist | pKi | 5.9 | 1,259 nM | Human | PMID 8935801 |
| 5-HT6 receptor HTR6 | Antagonist | pKi | 5.6 | 2,512 nM | Human | PMID 8522988 |
| 5-HT1A receptor HTR1A | Antagonist | pKi | — | — | Human | — |
| 5-HT1B receptor HTR1B | Antagonist | pKi | — | — | Human | — |
| 5-HT1D receptor HTR1D | Antagonist | pKi | — | — | Human | — |
| 5-HT2A receptor HTR2A | Inverse agonist | pKi | — | — | Human | — |
| 5-HT2C receptor HTR2C | Inverse agonist | pKi | — | — | Human | — |
| 5-HT6 receptor Htr6 | Inverse agonist | pKi | — | — | Rat | — |
| 5-HT7 receptor Htr7 | Inverse agonist | pKd | — | — | Rat | — |
| 5-HT7 receptor HTR7 | Inverse agonist | pKi | — | — | Human | — |
| H1 receptor HRH1 | Antagonist | pKi | — | — | Human | — |
| α1A-adrenoceptor ADRA1A | Antagonist | pKi | — | — | Human | — |
| α1B-adrenoceptor ADRA1B | Antagonist | pKi | — | — | Human | — |
Reading this. pKi, pEC50 and pIC50 are negative log molar values, so a higher number means a tighter interaction; the concentration column converts them for you. Values from non-human species are laboratory measurements and do not translate directly to human effect. Receptor affinity is not a dose — it describes what a molecule binds, not how much of it is safe to take.
Receptor data from the IUPHAR/BPS Guide to PHARMACOLOGY (v2026.2), licensed CC BY-SA 4.0. Matched to this substance by InChIKey.
Signs and Symptoms of Overdose Overdoses of risperidone typically do not result in fatalities, instead manifesting as symptoms that include drowsiness, sedation, tachycardia, hypotension, and extrapyramidal effects, reflecting an extension of its pharmacological action. Hyponatremia, prolonged QT interval, and seizures have been documented. Management of Overdose
Carcinogenicity
No indication of carcinogenicity to humans (not listed by IARC).
Liver injury risk
Low concern (rare serious cases reported)
Toxicity (DrugBank)
Symptoms of overdose include lethargy, dystonia/spasm, tachycardia, bradycardia, and seizures. LD50=57.7 mg/kg (rat, oral) and 34 mg/kg (rat, intravenous).
Experience Report Analysis
ErowidDemographics
Gender Distribution
Age Distribution
Reports Over Time
Effect Analysis
ErowidEffects aggregated from 11 experience reports (11 single-substance Erowid)
Effect Sentiment Distribution
Confidence Distribution
Each bar is the share of reports mentioning the effect; its whisker, and the band on the rows below, is the 95% interval: where the share could plausibly be with other reports of the same kind.
Too few reports for bars: these effects come from 11 single-substance Erowid reports, and a bar is drawn only from 20 reports or more. With fewer, a percentage cannot tell a common effect from a rare one. Counts are shown instead. Why 20?
Positive Effects 1
Adverse Effects 3
Show 2 neutral or unclassified mentions
Also reported in combinations. In the 22 Risperidone reports where another drug was taken too, 5 (22.7%) mention hospital, emergency services or an overdose, 2 (9.1%) a seizure and 9 (40.9%) psychosis. In the 11 single-substance reports: 5, 0 and 4. These are not in the figures above: they cannot be put down to Risperidone alone, and a mention is not always something that happened to the writer.
Dosage Distribution
Dose distribution from experience reports, one dose per report (the first listed). Doses above Q3 + 3×IQR, far above what people typically take, are left out of the median and range and listed under each route: most are real heavy doses or overdoses, not mistakes.
1 report gave a dose above the typical range (30 mg), so it is not in the figures above. It mentions hospital, emergency services or an overdose. Listing a dose here does not mean it is safe.
1 dose more than 50 times the median may be a typing or unit error and is not in the figures either: check the report.
Real-World Dose Distribution
ErowidFrom 39 of 45 recorded dose entries: those that state a weight (mg, g or µg), in routes with at least five of them. Values above Q3 + 3×IQR, far above what people typically take, are left out; they can include real heavy doses and overdoses, not only mistakes.
Oral (n=35)
Common Combinations
Most co-occurring substances, as a share of all 33 reports filed under Risperidone; whiskers are 95% intervals
Form / Preparation
Most common forms and preparations, as a share of the 13 reports that give one
Too few reports for bars: these forms come from 13 reports, and a bar is drawn only from 20 reports or more. With fewer, a percentage cannot tell a common effect from a rare one. Counts are shown instead. Why 20?
- Pill / Tablet 11 of 13
- Liquid 2 of 13
Body-Weight Dosing
Dose per kg of body weight, one dose per report (the first listed), from reports giving a weight of 30–250 kg. Doses above Q3 + 3×IQR, far above what people typically take, are left out of the median and range and listed under each route.
1 report gave a dose above the typical range (0.429 mg/kg), so it is not in the figures above. It mentions hospital, emergency services or an overdose. Listing a dose here does not mean it is safe.
1 dose more than 50 times the median may be a typing or unit error and is not in the figures either: check the report.
Show the reports
- 0.429 mg/kg · mentions hospital, emergency services or an overdose
Possibly a typing or unit error:
- 336.022 mg/kg · another drug taken too · mentions hospital, emergency services or an overdose
Redose Patterns
Redosing behavior across 25 reports