RISPERIDONE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H27FN4O2
Molecular Weight	410.4845
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=C(CCN2CCC(CC2)C3=NOC4=C3C=CC(F)=C4)C(=O)N5CCCCC5=N1

InChI

InChIKey=RAPZEAPATHNIPO-UHFFFAOYSA-N

InChI=1S/C23H27FN4O2/c1-15-18(23(29)28-10-3-2-4-21(28)25-15)9-13-27-11-7-16(8-12-27)22-19-6-5-17(24)14-20(19)30-26-22/h5-6,14,16H,2-4,7-13H2,1H3

HIDE SMILES / InChI

Molecular Formula	C23H27FN4O2
Molecular Weight	410.4845
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020272s077,020588s065,021346s055,021444s051lbl.pdf
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/risperidone.html http://www.wikidoc.org/index.php/Risperidone_(oral) http://www.rxlist.com/risperdal-drug.htm

Risperidone, a benzisoxazole derivative, is an atypical antipsychotic drug with high affinity for 5-hydrotryptamine (5-HT) and dopamine D2 receptors. It is FDA approved for the treatment of schizophrenia, bipolar mania, irritability associated with autistic disorder. Carbamazepine and other enzyme inducers decrease plasma concentrations of risperidone. Vice versa, Fluoxetine, paroxetine, and other CYP 2D6 enzyme inhibitors increase plasma concentrations of risperidone. Common adverse reactions include increased mortality in elderly patients with dementia-related psychosis, cerebrovascular adverse events, including stroke, in elderly patients with dementia-related psychosis, neuroleptic malignant syndrome, tardive dyskinesia , metabolic Changes (hyperglycemia and diabetes mellitus, dyslipidemia, weight gain), hyperprolactinemia, orthostatic hypotension, leukopenia, neutropenia, agranulocytosis, potential for cognitive and motor impairment, seizures, dysphagia, priapism, disruption of body temperature regulation.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Adrenergic receptor alpha-1 171 Target ID: CHEMBL2094251 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11132243	Antagonist 2849	2.7 nM [Kd]
Dopamine D2 receptor 311 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11132243	Antagonist 2849	3.8 nM [Kd]
Serotonin 1d (5-HT1d) receptor 53 Target ID: CHEMBL1983 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11132243	Antagonist 2849	3.9 nM [Kd]
Serotonin 2a (5-HT2a) receptor 237 Target ID: CHEMBL224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11132243 http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020272s077,020588s065,021346s055,021444s051lbl.pdf	Antagonist 2849	0.15 nM [Kd]

Conditions

Condition	Modality	Highest Phase	Product
Schizophrenia 305 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020272s077,020588s065,021346s055,021444s051lbl.pdf	Primary	Approved 8583	RISPERDAL Approved Use INDICATIONS & USAGE Risperidone tablets are indicated for the acute and maintenance treatment of schizophrenia [see Clinical Studies (14.1) Launch Date 1993
Acute manic or mixed episodes associated with Bipolar I disorder 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020272s077,020588s065,021346s055,021444s051lbl.pdf	Primary	Approved 8583	RISPERDAL Approved Use INDICATIONS & USAGE Risperidone tablets are indicated for the acute and maintenance treatment of schizophrenia [see Clinical Studies (14.1) Launch Date 1993
Irritability associated with autistic disorder 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020272s077,020588s065,021346s055,021444s051lbl.pdf	Primary	Approved 8583	RISPERDAL Approved Use INDICATIONS & USAGE Risperidone tablets are indicated for the acute and maintenance treatment of schizophrenia [see Clinical Studies (14.1) Launch Date 1993

C_max

Value	Dose	Co-administered	Analyte	Population
17 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11985287/	2 mg 2 times / day steady-state, oral dose: 2 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		RISPERIDONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
7.77 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25042870/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:		RISPERIDONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
83.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11985287/	2 mg 2 times / day steady-state, oral dose: 2 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		RISPERIDONE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
53.86 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25042870/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:		RISPERIDONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.88 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25042870/	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:		RISPERIDONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
20 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020588s046lbl.pdf	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:		RISPERIDONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
10% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020588s046lbl.pdf	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:		RISPERIDONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193	substrate 1388 inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 910 P-gp 1741	CYP3A5 446 CYP1A1 389 CYP1A2 1197 CYP2C8 810 CYP2C19 1119 P-gp 2052 BCRP 697 UGT 219

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
BCRP 985	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637613/ Page: 1.0	moderate [IC50 38.1 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021346s061lbl.pdf#page=37 Page: 37.0	weak	no (co-administration study) Comment: RISPERDAL did not significantly affect the pharmacokinetics of donepezil and galantamine, which are metabolized by CYP2D6 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021346s061lbl.pdf#page=37 Page: 37.0
P-gp 1932	inhibitor 4027 Sources: https://www.nature.com/articles/1301181	yes [IC50 15.78 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021346s061lbl.pdf#page=36 Page: 36.0	major	yes (co-administration study) Comment: Fluoxetine and paroxetine (CYP 2D6 inhibitors) have been shown to increase the plasma concentration of risperidone 2.5-2.8 fold and 3-9 fold, respectively Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021346s061lbl.pdf#page=36 Page: 36.0
CYP3A5 446	substrate 4014 Sources: https://link.springer.com/article/10.1007/PL00005334 Page: 3.0	minor
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15270204/ Page: 4.0	minor	yes (co-administration study) Comment: Carbamazepine co-administration with oral RISPERDAL decreased the steady-state plasma concentrations of risperidone by about 50%; Sources: https://pubmed.ncbi.nlm.nih.gov/15270204/ Page: 4.0
BCRP 697	substrate 4014 Sources: https://peerj.com/articles/2081/	no
CYP1A1 389	substrate 4014 Sources: https://link.springer.com/article/10.1007/PL00005334 Page: 3.0	no
CYP1A2 1197	substrate 4014 Sources: https://link.springer.com/article/10.1007/PL00005334 Page: 3.0	no
CYP2C19 1119	substrate 4014 Sources: https://link.springer.com/article/10.1007/PL00005334 Page: 3.0	no
CYP2C8 810	substrate 4014 Sources: https://link.springer.com/article/10.1007/PL00005334 Page: 3.0	no
CYP2C9 1193	substrate 4014 Sources: https://link.springer.com/article/10.1007/PL00005334 Page: 3.0	no
UGT 219	substrate 4014 Sources: https://academic.oup.com/ijnp/article-pdf/6/1/57/1794310/6-1-57.pdf Page: 8.0	no
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/16936711/ Page: 1.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubmed.ncbi.nlm.nih.gov/28265686/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:8871	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:8871
ChemicalBook	CB41565182	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB41565182
ChemicalBook	CB63154711	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB63154711
ChemicalBook	CB9131730	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9131730
eMolecules	902418	https://www.emolecules.com/cgi-bin/more?vid=902418
MolPort	MolPort-002-885-858	https://www.molport.com/shop/molecule-link/MolPort-002-885-858
MolPort	MolPort-047-151-613	https://www.molport.com/shop/molecule-link/MolPort-047-151-613
Selleck Chemicals	Risperidone(Risperdal)	http://www.selleckchem.com/products/Risperidone(Risperdal).html
ZINC	ZINC000000538312	http://zinc15.docking.org/substances/ZINC000000538312

PubMed

Title	Date	PubMed
Risperidone versus haloperidol in psychotic patients with disturbing neuroleptic-induced extrapyramidal symptoms: a double-blind, multi-center trial.	2000 Dec 15	11120421
[Neuropsychiatric symptoms in preventive antimalarial treatment with mefloquine: apropos of 2 cases].	2000 Jul-Aug	11064842
Risperidone-associated hyperprolactinemia.	2000 Nov-Dec	11155212
Risperidone and tardive dyskinesia: a case of blepharospasm.	2000 Oct	11037386
Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors.	2000 Oct	10991983
The effects of olanzapine, risperidone, and haloperidol on plasma prolactin levels in patients with schizophrenia.	2000 Sep	11048906
A naturalistic comparison of clozapine, risperidone, and olanzapine in the treatment of bipolar disorder.	2000 Sep	11030483
Acute dystonia induced by adding midodrine, a selective alpha 1 agonist, to risperidone in a patient with catatonic schizophrenia.	2000 Spring	11001613
Long-term risperidone for pervasive developmental disorder: efficacy, tolerability, and discontinuation.	2000 Summer	10933118
Antipsychotic medications and the elderly: effects on cognition and implications for use.	2001	11232738
Olanzapine: an updated review of its use in the management of schizophrenia.	2001	11217867
Atypical antipsychotics: new directions and new challenges in the treatment of schizophrenia.	2001	11160792
Effective treatment of aggression and impulsivity in antisocial personality disorder with risperidone.	2001 Apr	11285097
Risperidone-induced retrograde ejaculation.	2001 Apr	11282707
An MRI study of basal ganglia volumes in first-episode schizophrenia patients treated with risperidone.	2001 Apr	11282699
Novel treatments for bipolar disorder.	2001 Apr	11281816
Dynamic dopamine-antagonist interactions at recombinant human dopamine D(2short) receptor: dopamine-bound versus antagonist-bound receptor states.	2001 Apr	11259537
Protein thiol oxidation by haloperidol results in inhibition of mitochondrial complex I in brain regions: comparison with atypical antipsychotics.	2001 Apr	11222923
Health care utilization in patients with schizophrenia maintained on atypical versus conventional antipsychotics.	2001 Feb	11294482
Dose relationship of limbic-cortical D2-dopamine receptor occupancy with risperidone.	2001 Feb	11292000
Treatment of psychogenic polydipsia: comparison of risperidone and olanzapine, and the effects of an adjunctive angiotensin-II receptor blocking drug (irbesartan).	2001 Feb	11270459
Addition of risperidone to clozapine therapy in chronically psychotic inpatients.	2001 Feb	11247102
Priapism associated with polypharmacy.	2001 Feb	11247100
Weight gain with risperidone among patients with mental retardation: effect of calorie restriction.	2001 Feb	11247096
Long-term treatment of chronic schizophrenia with risperidone: a study with plasma levels.	2001 Feb	11246293
A case of risperidone-induced stuttering.	2001 Feb	11199937
Atypical antipsychotics and cardiovascular risk in schizophrenic patients.	2001 Feb	11199934
Adverse drug interaction between risperidone and carbamazepine in a patient with chronic schizophrenia and deficient CYP2D6 activity.	2001 Feb	11199933
Hyperthermia and chronic pancerebellar syndrome after cocaine abuse.	2001 Feb 26	11252123
Receptor-mediated regulation of serotonin output in the rat dorsal raphe nucleus: effects of risperidone.	2001 Jan	11271402
Bodyweight gain with atypical antipsychotics. A comparative review.	2001 Jan	11219487
Risperidone-induced cholestatic hepatitis.	2001 Jan	11204814
Does risperidone have a place in the treatment of nonschizophrenic patients?	2001 Jan	11195255
Relationship between plasma risperidone and 9-hydroxyrisperidone concentrations and clinical response in patients with schizophrenia.	2001 Jan 1	11205425
Consistency of atypical antipsychotic superiority to placebo in recent clinical trials.	2001 Jan 1	11163781
Antipsychotic drugs classified by their effects on the release of dopamine and noradrenaline in the prefrontal cortex and striatum.	2001 Jan 26	11165224
[Viewpoint of schizophrenic patients: a European survey].	2001 Jan-Feb	11294036
Effects of dopamine antagonists with different receptor blockade profiles on morphine-induced place preference in male mice.	2001 Jun	11275296
Effectiveness of ECT combined with risperidone against aggression in schizophrenia.	2001 Mar	11281510
Suspected induction of a pyoderma gangrenosum-like eruption due to sulpiride treatment.	2001 Mar	11270303
The evaluation of multiple surrogate endpoints.	2001 Mar	11252622
5-HT(2A) and D(2) receptor blockade increases cortical DA release via 5-HT(1A) receptor activation: a possible mechanism of atypical antipsychotic-induced cortical dopamine release.	2001 Mar	11238736
Fixed-dosed risperidone in mania: an open experimental trial.	2001 Mar	11236068
Does fast dissociation from the dopamine d(2) receptor explain the action of atypical antipsychotics?: A new hypothesis.	2001 Mar	11229973
Pharmacological characterization of locomotor sensitization induced by chronic phencyclidine administration.	2001 Mar	11181923
Estrogen - a potential treatment for schizophrenia.	2001 Mar 1	11278160
Effects of olanzapine and other antipsychotics on cognitive function in chronic schizophrenia: a longitudinal study.	2001 Mar 1	11278151
Short-term inpatient pharmacotherapy of schizophrenia.	2001 May-Jun	11287404
Risperidone addition and psychotic exacerbation.	2001 Winter	11207341
Full remission of panic attacks in a schizophrenic patient after switching from haloperidol to risperidone.	2001 Winter	11207340

Patents

Sample Use Guides

In Vivo Use Guide

Initial dosing is generally 2 mg/day. Dose increases should then occur at intervals not less than 24 hours, in increments of 1–2 mg/day, as tolerated, to a recommended dose of 4–8 mg/day. Effective dose range - 0.5-16 mg (disease dependent).

Route of Administration: Other

In Vitro Use Guide

Measurement of ATP contents in the neuronal cell line showed significantly increased levels after a 24-h treatment with 25 microg/mL risperidone.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 09:06:18 GMT 2025` Edited by `admin` on `Wed Apr 02 09:06:18 GMT 2025`
Record UNII	L6UH7ZF8HC
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

N05AX08

Preferred Name

English

RISPERIDONE

Official Name

English

RISPERIDONE [EP MONOGRAPH]

Common Name

English

Risperidone [WHO-DD]

Common Name

English

R-64766

Code

English

R 64 766

Code

English

RISPERIDONE [EP IMPURITY]

Common Name

English

RISPERIDONE [USAN]

Common Name

English

RISPERIDONE [USP MONOGRAPH]

Common Name

English

RISPERIDONE [USP IMPURITY]

Common Name

English

RISPERIDONE [ORANGE BOOK]

Common Name

English

R-64,766

Code

English

PERSERIS

Brand Name

English

RISPERIDONE [HSDB]

Common Name

English

RISPERIDONE [USP-RS]

Common Name

English

RISPERIDONE [MART.]

Common Name

English

RCN3028

Code

English

RISPERDAL

Brand Name

English

RCN-3028

Code

English

RISPERIDONE [JAN]

Common Name

English

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

Systematic Name

English

R-64-766

Code

English

NSC-759895

Code

English

UZEDY

Brand Name

English

LY-03004

Code

English

risperidone [INN]

Common Name

English

RYKINDO

Brand Name

English

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-

Systematic Name

English

RISPERIDONE [VANDF]

Common Name

English

RISPERIDONE [MI]

Common Name

English

RISVAN

Brand Name

English

Classification Tree Code System Code

WHO-ATC

N05AX08