U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C21H21ClN4OS.CH4O3S.3H2O
Molecular Weight 563.0901
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ZIPRASIDONE MESYLATE

SMILES

c1ccc2c(c1)c(ns2)N3CCN(CCc4cc5CC(=Nc5cc4Cl)O)CC3.CS(=O)(=O)O.O.O.O

InChI

InChIKey=WLQZEFFFIUHSJB-UHFFFAOYSA-N
InChI=1S/C21H21ClN4OS.CH4O3S.3H2O/c22-17-13-18-15(12-20(27)23-18)11-14(17)5-6-25-7-9-26(10-8-25)21-16-3-1-2-4-19(16)28-24-21;1-5(2,3)4;;;/h1-4,11,13H,5-10,12H2,(H,23,27);1H3,(H,2,3,4);3*1H2

HIDE SMILES / InChI

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C21H21ClN4OS
Molecular Weight 412.9374
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula CH4O3S
Molecular Weight 96.1068
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: description was created based on several sources, including https://effectivehealthcare.ahrq.gov/ehc/products/150/786/CER43_Off-LabelAntipsychotics_execsumm_20110928.pdf

Ziprasidone is atypical antipsychotic, approved by the U.S. Food and Drug Administration for the treatment of schizophrenia, and acute mania and mixed states associated with bipolar disorder. Intramuscilar injections of Ziprasidone are indicated for rapid control of the agitation in schizophrenic patients. Ziprasidone is used off-label for treatment of major depressive disorder, anxiety, obsessive compulsive disorder, borderline personality disorder. Ziprasidone functions as an antagonist at the D2, 5HT2A, and 5HT1D receptors, and as an agonist at the 5HT1A receptor.

Originator

Curator's Comment:: # Pfizer

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
GEODON

Approved Use

Ziprasidone hydrochloride capsule is an atypical antipsychotic. In choosing among treatments, prescribers should be aware of the capacity of ziprasidone hydrochloride capsule to prolong the QT interval and may consider the use of other drugs first.

Launch Date

9.8133121E11
Primary
GEODON

Approved Use

Ziprasidone hydrochloride capsule is an atypical antipsychotic. In choosing among treatments, prescribers should be aware of the capacity of ziprasidone hydrochloride capsule to prolong the QT interval and may consider the use of other drugs first. Ziprasidone intramuscular is indicated for the treatment of acute agitation in schizophrenic patients for whom treatment with ziprasidone is appropriate and who need intramuscular antipsychotic medication for rapid control of the agitation. “Psychomotor agitation” is defined in DSM-IV as “excessive motor activity associated with a feeling of inner tension.”

Launch Date

9.8133121E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
51 ng/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZIPRASIDONE serum
Homo sapiens
population: UNHEALTHY
age: ADOLESCENT
sex: FEMALE / MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
457 ng × h/mL
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZIPRASIDONE serum
Homo sapiens
population: UNHEALTHY
age: ADOLESCENT
sex: FEMALE / MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
4.1 h
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ZIPRASIDONE serum
Homo sapiens
population: UNHEALTHY
age: ADOLESCENT
sex: FEMALE / MALE
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
ZIPRASIDONE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
4480 mg single, oral
Overdose
Dose: 4480 mg
Route: oral
Route: single
Dose: 4480 mg
Co-administed with::
Clomethiazole(192 mg)
Sources:
unhealthy, 22 years
n = 1
Health Status: unhealthy
Condition: Paranoid Schizophrenia
Age Group: 22 years
Sex: M
Population Size: 1
Sources:
Disc. AE: Sedation, Hypotension...
AEs leading to
discontinuation/dose reduction:
Sedation (1 patient)
Hypotension (1 patient)
Sources:
20 mg single, oral
Overdose
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources:
healthy, 30 month
n = 1
Health Status: healthy
Age Group: 30 month
Sex: F
Population Size: 1
Sources:
Disc. AE: Respiratory depression...
AEs leading to
discontinuation/dose reduction:
Respiratory depression (1 patient)
Sources:
780 mg single, oral
Overdose
Dose: 780 mg
Route: oral
Route: single
Dose: 780 mg
Sources:
unhealthy, 31 years
n = 1
Health Status: unhealthy
Condition: Mixed personality disorder
Age Group: 31 years
Sex: M
Population Size: 1
Sources:
Disc. AE: Drowsiness...
AEs leading to
discontinuation/dose reduction:
Drowsiness (1 patient)
Sources:
1120 mg single, oral
Overdose
Dose: 1120 mg
Route: oral
Route: single
Dose: 1120 mg
Sources:
unhealthy, 35 years
n = 1
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 35 years
Sex: M
Population Size: 1
Sources:
4400 mg single, oral
Overdose
Dose: 4400 mg
Route: oral
Route: single
Dose: 4400 mg
Co-administed with::
Clomethiazole(768 mg)
flunitrazepam(4 mg)
Sources:
unhealthy, 57 years
n = 1
Health Status: unhealthy
Condition: Manic-depressive disorder
Age Group: 57 years
Sex: F
Population Size: 1
Sources:
Disc. AE: Drowsiness, Tremor...
AEs leading to
discontinuation/dose reduction:
Drowsiness (1 patient)
Tremor (1 patient)
Anxiety (1 patient)
Sources:
20 mg 2 times / day steady, intramuscular
Studied dose
Dose: 20 mg, 2 times / day
Route: intramuscular
Route: steady
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 60 – 81 years
n = 21
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 60 – 81 years
Sex: M+F
Population Size: 21
Sources:
Other AEs: Blurred vision, Sedation...
Other AEs:
Blurred vision (1 patient)
Sedation (1 patient)
Sources:
40 mg 1 times / day steady, oral
Studied dose
Dose: 40 mg, 1 times / day
Route: oral
Route: steady
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 7 – 17 years
n = 28
Health Status: unhealthy
Condition: Tourette's syndrome
Age Group: 7 – 17 years
Sex: M+F
Population Size: 28
Sources:
Other AEs: Somnolence, Akathisia...
Other AEs:
Somnolence (1 patient)
Akathisia (1 patient)
Sources:
20 mg single, oral
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources:
unhealthy, 7-16 years
n = 24
Health Status: unhealthy
Condition: Tourette's disorder or chronic tic disorder
Age Group: 7-16 years
Sex: M+F
Population Size: 24
Sources:
Other AEs: Somnolence, Syncope hypotensive...
Other AEs:
Somnolence (16 patients)
Syncope hypotensive (2 patients)
Sources:
AEs

AEs

AESignificanceDosePopulation
Hypotension 1 patient
Disc. AE
4480 mg single, oral
Overdose
Dose: 4480 mg
Route: oral
Route: single
Dose: 4480 mg
Co-administed with::
Clomethiazole(192 mg)
Sources:
unhealthy, 22 years
n = 1
Health Status: unhealthy
Condition: Paranoid Schizophrenia
Age Group: 22 years
Sex: M
Population Size: 1
Sources:
Sedation 1 patient
Disc. AE
4480 mg single, oral
Overdose
Dose: 4480 mg
Route: oral
Route: single
Dose: 4480 mg
Co-administed with::
Clomethiazole(192 mg)
Sources:
unhealthy, 22 years
n = 1
Health Status: unhealthy
Condition: Paranoid Schizophrenia
Age Group: 22 years
Sex: M
Population Size: 1
Sources:
Respiratory depression 1 patient
Disc. AE
20 mg single, oral
Overdose
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources:
healthy, 30 month
n = 1
Health Status: healthy
Age Group: 30 month
Sex: F
Population Size: 1
Sources:
Drowsiness 1 patient
Disc. AE
780 mg single, oral
Overdose
Dose: 780 mg
Route: oral
Route: single
Dose: 780 mg
Sources:
unhealthy, 31 years
n = 1
Health Status: unhealthy
Condition: Mixed personality disorder
Age Group: 31 years
Sex: M
Population Size: 1
Sources:
Anxiety 1 patient
Disc. AE
4400 mg single, oral
Overdose
Dose: 4400 mg
Route: oral
Route: single
Dose: 4400 mg
Co-administed with::
Clomethiazole(768 mg)
flunitrazepam(4 mg)
Sources:
unhealthy, 57 years
n = 1
Health Status: unhealthy
Condition: Manic-depressive disorder
Age Group: 57 years
Sex: F
Population Size: 1
Sources:
Drowsiness 1 patient
Disc. AE
4400 mg single, oral
Overdose
Dose: 4400 mg
Route: oral
Route: single
Dose: 4400 mg
Co-administed with::
Clomethiazole(768 mg)
flunitrazepam(4 mg)
Sources:
unhealthy, 57 years
n = 1
Health Status: unhealthy
Condition: Manic-depressive disorder
Age Group: 57 years
Sex: F
Population Size: 1
Sources:
Tremor 1 patient
Disc. AE
4400 mg single, oral
Overdose
Dose: 4400 mg
Route: oral
Route: single
Dose: 4400 mg
Co-administed with::
Clomethiazole(768 mg)
flunitrazepam(4 mg)
Sources:
unhealthy, 57 years
n = 1
Health Status: unhealthy
Condition: Manic-depressive disorder
Age Group: 57 years
Sex: F
Population Size: 1
Sources:
Blurred vision 1 patient
20 mg 2 times / day steady, intramuscular
Studied dose
Dose: 20 mg, 2 times / day
Route: intramuscular
Route: steady
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 60 – 81 years
n = 21
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 60 – 81 years
Sex: M+F
Population Size: 21
Sources:
Sedation 1 patient
20 mg 2 times / day steady, intramuscular
Studied dose
Dose: 20 mg, 2 times / day
Route: intramuscular
Route: steady
Dose: 20 mg, 2 times / day
Sources:
unhealthy, 60 – 81 years
n = 21
Health Status: unhealthy
Condition: Schizophrenia
Age Group: 60 – 81 years
Sex: M+F
Population Size: 21
Sources:
Akathisia 1 patient
40 mg 1 times / day steady, oral
Studied dose
Dose: 40 mg, 1 times / day
Route: oral
Route: steady
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 7 – 17 years
n = 28
Health Status: unhealthy
Condition: Tourette's syndrome
Age Group: 7 – 17 years
Sex: M+F
Population Size: 28
Sources:
Somnolence 1 patient
40 mg 1 times / day steady, oral
Studied dose
Dose: 40 mg, 1 times / day
Route: oral
Route: steady
Dose: 40 mg, 1 times / day
Sources:
unhealthy, 7 – 17 years
n = 28
Health Status: unhealthy
Condition: Tourette's syndrome
Age Group: 7 – 17 years
Sex: M+F
Population Size: 28
Sources:
Somnolence 16 patients
20 mg single, oral
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources:
unhealthy, 7-16 years
n = 24
Health Status: unhealthy
Condition: Tourette's disorder or chronic tic disorder
Age Group: 7-16 years
Sex: M+F
Population Size: 24
Sources:
Syncope hypotensive 2 patients
20 mg single, oral
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources:
unhealthy, 7-16 years
n = 24
Health Status: unhealthy
Condition: Tourette's disorder or chronic tic disorder
Age Group: 7-16 years
Sex: M+F
Population Size: 24
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >100 uM]
no [IC50 >133 uM]
no [IC50 >133 uM]
no [IC50 >133 uM]
no [IC50 >133 uM]
no
yes [IC50 5.8 uM]
no (co-administration study)
Comment: Estimated Cfree,plasma = 0.29-0.73 nM (80mg BID); Coadministration of Ziprasidone had no effect on the urinary Dextromethorphan/Dextrophan ratio.
Page: 16, (ClinPharm) 16, (ClinPharm4) 58-60
yes [Ki 64 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
likely
major
yes (co-administration study)
Comment: Ketoconazole inhibited formation of Ziprasidone sulfoxide by 77% in vitro.; Coadministration of Ketoconazoke (strong CYP3A4 inhibitor) increased Ziprasidone AUC and Cmax by about 30%. Coadministration of Carbamazepine (strong CYP3A4 inducer) decreased Ziprasidone AUC by 36% and Cmax by 27%.
Page: 15-16, (ClinPhar) 15-16, (ClinPharm3) 65-66, (ClinPharm4) 35-38, 64-66
minor
yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Inverse agonist activity of atypical antipsychotic drugs at human 5-hydroxytryptamine2C receptors.
2000 Oct
Focus on ziprasidone.
2001
Antipsychotic medications and the elderly: effects on cognition and implications for use.
2001
Atypical antipsychotics: new directions and new challenges in the treatment of schizophrenia.
2001
Antipsychotic metabolic effects: weight gain, diabetes mellitus, and lipid abnormalities.
2001 Apr
Cost effectiveness of the newer atypical antipsychotics: a review of the pharmacoeconomic research evidence.
2001 Jan
Antipsychotic drugs classified by their effects on the release of dopamine and noradrenaline in the prefrontal cortex and striatum.
2001 Jan 26
Ziprasidone approved.
2001 Jun
New schizophrenia drug.
2001 May-Jun
Ziprasidone: profile on safety.
2001 Oct
Med-psych drug-drug interactions update.
2001 Sep-Oct
Antipsychotic-related QTc prolongation, torsade de pointes and sudden death.
2002
Advances in atypical antipsychotics for the treatment of schizophrenia: new formulations and new agents.
2002
Effects of newer antipsychotics on extrapyramidal function.
2002
The anxiolytic effect of the novel antipsychotic ziprasidone compared with diazepam in subjects anxious before dental surgery.
2002 Apr
Priapism associated with two atypical antipsychotic agents.
2002 Aug
Case series: use of ziprasidone for maladaptive symptoms in youths with autism.
2002 Aug
Tardive dyskinesia and ziprasidone.
2002 Aug
A comparison of the receptor binding and HERG channel affinities for a series of antipsychotic drugs.
2002 Aug 16
Recent developments in pharmacotherapy for the acutely psychotic patient.
2002 Dec
Aripiprazole: profile on efficacy and safety.
2002 Dec
New drugs 2002, part 1.
2002 Jan
Ziprasidone hydrochloride.
2002 Jan 1
Brief report on Ziprasidone.
2002 Jul
The value of atypical antipsychotics in the treatment of schizophrenia.
2002 Jul
A 28-week comparison of ziprasidone and haloperidol in outpatients with stable schizophrenia.
2002 Jun
Prolongation of QTc interval and antipsychotics.
2002 Jun
Ziprasidone: the fifth atypical antipsychotic.
2002 May
The role of atypical antipsychotics in the treatment of delirium.
2002 May-Jun
A 1-year, double-blind, placebo-controlled trial of ziprasidone 40, 80 and 160 mg/day in chronic schizophrenia: the Ziprasidone Extended Use in Schizophrenia (ZEUS) study.
2002 Sep
Comprehensive understanding of schizophrenia and its treatment.
2002 Sep 1
Clinical issues associated with maintenance treatment of patients with schizophrenia.
2002 Sep 1
Continuum of care: stabilizing the acutely agitated patient.
2002 Sep 1
Cataract occurrence with antipsychotic drugs.
2002 Sep-Oct
Optimal dosing of atypical antipsychotics in adults: a review of the current evidence.
2002 Sep-Oct
Clinical significance of drug binding, protein binding, and binding displacement drug interactions.
2002 Summer
Safety and tolerability: how do newer generation "atypical" antipsychotics compare?
2002 Winter
Antipsychotic-induced hyperprolactinemia and sexual dysfunction.
2002 Winter
Ziprasidone-associated galactorrhea in a female teenager.
2003 Jan
Patents

Sample Use Guides

For treatment of schizophrenia, GEODON capsules should be administered at an initial daily dose of 20 mg BID with food. Daily dosage may subsequently be adjusted on the basis of individual clinical status up to 80 mg BID. Systematic evaluation of ziprasidone has shown that its efficacy in schizophrenia is maintained for periods of up to 52 weeks at a dose of 20 to 80 mg BID. For treatment of bipolar mania, oral ziprasidone should be administered at an initial daily dose of 40 mg BID with food. The dose should then be increased to 60 mg or 80 mg BID on the second day of treatment and subsequently adjusted on the basis of toleration and efficacy within the range 40-80 mg BID. The recommended dose for intramuscular administration is 10 to 20 mg administered as required up to a maximum dose of 40 mg per day. Doses of 10 mg may be administered every two hours; doses of 20 mg may be administered every four hours up to a maximum of 40 mg/day.
Route of Administration: Other
In Vitro Use Guide
Standard receptor-binding methods were used to label dopamine D2 receptors using [3H]spiperone. Briefly, rats were sacrificed by decapitation and the brains rapidly removed. The corpus striatum was dissected and homogenized in 20 vol at 50 mM Tris HCl (pH 7.2) buffer using a Brinkman Polytron homogenizer (setting 7 for 15 s). The homogenate was centrifuged for 10 min at 40000g. The pellet was resuspended in fresh ice-cold 50 mM Tris (pH 7.2) buffer with the Polytron homogenizer and recentrifuged. The final pellet was resuspended in 50 mM Tris HCl buffer (pH 7.2) containing 1 mM MgCl2 and 100 mM NaCl. Assays were initiated by the addition of tissue to tubes containing [3H]spiperone (0.2 nM) and drug or buffer in a final volume of 1 mL. Blocking agents (500 nM cinanserin and 1 mM prazosin) were present to prevent [3H]spiperone from labeling 5-HT2 and R1 noradrenergic receptors. Nonspecific binding was defined as the radioligand bound in the presence of 10 uM (+)-butaclamol. After a 15 min incubation at 37 °C, tissue samples were filtered onto Whatman GF/B glass fiber filters using a Brandel harvester and rinsed two times with 5 mL of ice-cold 50 mM Tris HCl (pH 7.4) buffer. Filters were soaked in 10 mL of Ready-Safe (Beckman Instruments), and the radioactivity was quantified using liquid scintillation counting. Ziprasidone binds to D2 receptors with pKi of 8.32 nM.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:07:09 UTC 2021
Edited
by admin
on Fri Jun 25 21:07:09 UTC 2021
Record UNII
3X6SAX83JZ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ZIPRASIDONE MESYLATE
ORANGE BOOK   USAN   VANDF  
USAN  
Official Name English
5-(2-(4-(1,2-BENZISOTHIAZOL-3-YL)-1-PIPERAZINYL)ETHYL)-6-CHLORO-2-INDOLINONE MONOMETHANESULFONATE, TRIHYDRATE
Systematic Name English
ZIPRASIDONE MESYLATE [ORANGE BOOK]
Common Name English
ZIPRASIDONE MESYLATE [USAN]
Common Name English
2H-INDOL-2-ONE, 5-(2-(4-(1,2-BENZISOTHIAZOL-3-YL)-1-PIPERAZINYL)ETHYL)-6-CHLORO-1,3-DIHYDRO-, MONOMETHANESULFONATE, TRIHYDRATE
Systematic Name English
NSC-760351
Code English
ZIPRASIDONE MESILATE [MART.]
Common Name English
ZIPRASIDONE MESILATE TRIHYDRATE [EP MONOGRAPH]
Common Name English
CP-88, 059-27
Code English
ZIPRASIDONE MESYLATE [VANDF]
Common Name English
CP-88059-27
Code English
ZIPRASIDONE MESILATE TRIHYDRATE
Common Name English
CP-8805927
Code English
2H-INDOL-2-ONE, 5-(2-(4-(1,2-BENZISOTHIAZOL-3-YL)-1-PIPERAZINYL)ETHYL)-6-CHLORO-1,3-DIHYDRO-, METHANESULFONATE, HYDRATE (1:1:3)
Systematic Name English
Code System Code Type Description
RXCUI
353116
Created by admin on Fri Jun 25 21:07:09 UTC 2021 , Edited by admin on Fri Jun 25 21:07:09 UTC 2021
PRIMARY RxNorm
ChEMBL
CHEMBL708
Created by admin on Fri Jun 25 21:07:09 UTC 2021 , Edited by admin on Fri Jun 25 21:07:09 UTC 2021
PRIMARY
FDA UNII
3X6SAX83JZ
Created by admin on Fri Jun 25 21:07:09 UTC 2021 , Edited by admin on Fri Jun 25 21:07:09 UTC 2021
PRIMARY
CAS
199191-69-0
Created by admin on Fri Jun 25 21:07:09 UTC 2021 , Edited by admin on Fri Jun 25 21:07:09 UTC 2021
PRIMARY
EVMPD
SUB72091
Created by admin on Fri Jun 25 21:07:09 UTC 2021 , Edited by admin on Fri Jun 25 21:07:09 UTC 2021
PRIMARY
NCI_THESAURUS
C48032
Created by admin on Fri Jun 25 21:07:09 UTC 2021 , Edited by admin on Fri Jun 25 21:07:09 UTC 2021
PRIMARY
PUBCHEM
656685
Created by admin on Fri Jun 25 21:07:09 UTC 2021 , Edited by admin on Fri Jun 25 21:07:09 UTC 2021
PRIMARY
DRUG BANK
DBSALT000811
Created by admin on Fri Jun 25 21:07:09 UTC 2021 , Edited by admin on Fri Jun 25 21:07:09 UTC 2021
PRIMARY
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IMPURITY -> PARENT
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IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
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