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

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-1 169 Target ID: CHEMBL2094251 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11132243	Antagonist 2778	2.7 nM [Kd]
Dopamine D2 receptor 297 Target ID: CHEMBL217 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11132243	Antagonist 2778	3.8 nM [Kd]
Serotonin 1d (5-HT1d) receptor 52 Target ID: CHEMBL1983 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11132243	Antagonist 2778	3.9 nM [Kd]
Serotonin 2a (5-HT2a) receptor 231 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 2778	0.15 nM [Kd]

Conditions

Condition	Modality	Highest Phase	Product
Schizophrenia 298 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020272s077,020588s065,021346s055,021444s051lbl.pdf	Primary	Approved 8429	RISPERDAL Approved Use INDICATIONS & USAGE Risperidone tablets are indicated for the acute and maintenance treatment of schizophrenia [see Clinical Studies (14.1) Launch Date 7.5712319E11
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 8429	RISPERDAL Approved Use INDICATIONS & USAGE Risperidone tablets are indicated for the acute and maintenance treatment of schizophrenia [see Clinical Studies (14.1) Launch Date 7.5712319E11
Irritability associated with autistic disorder 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020272s077,020588s065,021346s055,021444s051lbl.pdf	Primary	Approved 8429	RISPERDAL Approved Use INDICATIONS & USAGE Risperidone tablets are indicated for the acute and maintenance treatment of schizophrenia [see Clinical Studies (14.1) Launch Date 7.5712319E11

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
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
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

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

Doses

Dose	Population	Adverse events
16 mg 1 times / day multiple, oral (max) Recommended Dose: 16 mg, 1 times / day Route: oral Route: multiple Dose: 16 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020272s056,020588s044,021346s033,021444s03lbl.pdf	unhealthy, adult n = 198 Health Status: unhealthy Condition: Schizophrenia Age Group: adult Population Size: 198 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020272s056,020588s044,021346s033,021444s03lbl.pdf	Disc. AE: Dizziness, Agitation... AEs leading to discontinuation/dose reduction: Dizziness (1%) Agitation (1%) Somnolence (0.5%) Hypotension postural (0.5%) Tachycardia (0.5%) Akathisia (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020272s056,020588s044,021346s033,021444s03lbl.pdf
6 mg 1 times / day multiple, oral (max) Recommended Dose: 6 mg, 1 times / day Route: oral Route: multiple Dose: 6 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020272s056,020588s044,021346s033,021444s03lbl.pdf	unhealthy, adult n = 448 Health Status: unhealthy Condition: Bipolar Mania Age Group: adult Population Size: 448 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020272s056,020588s044,021346s033,021444s03lbl.pdf	Disc. AE: Parkinsonism, Somnolence... AEs leading to discontinuation/dose reduction: Parkinsonism (0.4%) Somnolence (0.2%) Dizziness (0.2%) Dystonia (0.2%) SGOT increased (0.2%) SGPT increased (0.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020272s056,020588s044,021346s033,021444s03lbl.pdf
8 mg 1 times / day multiple, oral (max) Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020272s056,020588s044,021346s033,021444s03lbl.pdf	unhealthy, adult n = 366 Health Status: unhealthy Condition: Schizophrenia Age Group: adult Population Size: 366 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020272s056,020588s044,021346s033,021444s03lbl.pdf	Disc. AE: Dizziness, Nausea... AEs leading to discontinuation/dose reduction: Dizziness (1.4%) Nausea (1.4%) Agitation (1.1%) Parkinsonism (0.8%) Somnolence (0.8%) Dystonia (0.5%) Abdominal pain (0.5%) Hypotension postural (0.3%) Tachycardia (0.3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020272s056,020588s044,021346s033,021444s03lbl.pdf
6 mg 1 times / day multiple, oral (max) Recommended Dose: 6 mg, 1 times / day Route: oral Route: multiple Dose: 6 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020272s056,020588s044,021346s033,021444s03lbl.pdf	unhealthy, child n = 106 Health Status: unhealthy Condition: Schizophrenia Age Group: child Population Size: 106 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020272s056,020588s044,021346s033,021444s03lbl.pdf	Disc. AE: Somnolence, Dizziness... AEs leading to discontinuation/dose reduction: Somnolence (2%) Dizziness (2%) Anorexia (1%) Anxiety (1%) Ataxia (1%) Hypotension (1%) Palpitation (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020272s056,020588s044,021346s033,021444s03lbl.pdf
6 mg 1 times / day multiple, oral (max) Recommended Dose: 6 mg, 1 times / day Route: oral Route: multiple Dose: 6 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020272s056,020588s044,021346s033,021444s03lbl.pdf	unhealthy, child n = 111 Health Status: unhealthy Condition: Bipolar Mania Age Group: child Population Size: 111 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020272s056,020588s044,021346s033,021444s03lbl.pdf	Disc. AE: Somnolence, Nausea... AEs leading to discontinuation/dose reduction: Somnolence (5%) Nausea (3%) Abdominal pain (2%) Vomiting (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020272s056,020588s044,021346s033,021444s03lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 699 P-gp 1461	CYP3A5 395 CYP1A1 349 CYP1A2 1054 CYP2C8 693 CYP2C19 991 P-gp 1537 BCRP 561 UGT 192

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
BCRP 773	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2637613/ Page: 1.0	moderate [IC50 38.1 uM]
CYP2D6 1891	inhibitor 3277 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 1650	inhibitor 3277 Sources: https://www.nature.com/articles/1301181	yes [IC50 15.78 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2D6 1217	substrate 3367 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 395	substrate 3367 Sources: https://link.springer.com/article/10.1007/PL00005334 Page: 3.0	minor
CYP3A4 1737	substrate 3367 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 561	substrate 3367 Sources: https://peerj.com/articles/2081/	no
CYP1A1 349	substrate 3367 Sources: https://link.springer.com/article/10.1007/PL00005334 Page: 3.0	no
CYP1A2 1054	substrate 3367 Sources: https://link.springer.com/article/10.1007/PL00005334 Page: 3.0	no
CYP2C19 991	substrate 3367 Sources: https://link.springer.com/article/10.1007/PL00005334 Page: 3.0	no
CYP2C8 693	substrate 3367 Sources: https://link.springer.com/article/10.1007/PL00005334 Page: 3.0	no
CYP2C9 1037	substrate 3367 Sources: https://link.springer.com/article/10.1007/PL00005334 Page: 3.0	no
UGT 192	substrate 3367 Sources: https://academic.oup.com/ijnp/article-pdf/6/1/57/1794310/6-1-57.pdf Page: 8.0	no
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16936711/ Page: 1.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 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
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
eMolecules	902418	https://www.emolecules.com/cgi-bin/more?vid=902418

PubMed

Title	Date	PubMed
Use of the dopamine agonists bromocriptine and cabergoline in the management of risperidone-induced hyperprolactinemia in patients with psychotic disorders.	2000 Dec	11194712
Serotonin and dopamine antagonism in obsessive-compulsive disorder: effect of atypical antipsychotic drugs.	2000 Nov	11147933
Risperidone-associated hyperprolactinemia.	2000 Nov-Dec	11155212
Weight change and atypical antipsychotic treatment in patients with schizophrenia.	2001	11232752
Evidence for the effectiveness of olanzapine among patients nonresponsive and/or intolerant to risperidone.	2001	11232749
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
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
Drug induced akathisia, suicidal ideation and its treatment in the elderly.	2001 Feb	11241732
Tolerability and effectiveness of atypical antipsychotics in male geriatric inpatients.	2001 Feb	11241729
Combination risperidone and quetiapine therapy in refractory schizophrenia.	2001 Feb	11221496
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
Rehospitalization rates of chronically ill schizophrenic patients discharged on a regimen of risperidone, olanzapine, or conventional antipsychotics.	2001 Feb	11156809
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
Risperidone versus pimozide in Tourette's disorder: a comparative double-blind parallel-group study.	2001 Jan	11235929
Acute and long-term treatment of catatonia with risperidone.	2001 Jan	11229618
Bodyweight gain with atypical antipsychotics. A comparative review.	2001 Jan	11219487
Risperidone-induced cholestatic hepatitis.	2001 Jan	11204814
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
Hyperfunction of dopaminergic and serotonergic neuronal systems in mice lacking the NMDA receptor epsilon1 subunit.	2001 Jan 15	11160454
[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.

Name

Type

Language

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

N05AX08

Code

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

Classification Tree Code System Code

WHO-ATC

N05AX08