Details
Stereochemistry | ACHIRAL |
Molecular Formula | C20H24N4O4 |
Molecular Weight | 384.429 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCN1C2=C(N(C)C(\C=C\C3=CC(OC)=C(OC)C=C3)=N2)C(=O)N(CC)C1=O
InChI
InChIKey=IQVRBWUUXZMOPW-PKNBQFBNSA-N
InChI=1S/C20H24N4O4/c1-6-23-18-17(19(25)24(7-2)20(23)26)22(3)16(21-18)11-9-13-8-10-14(27-4)15(12-13)28-5/h8-12H,6-7H2,1-5H3/b11-9+
Molecular Formula | C20H24N4O4 |
Molecular Weight | 384.429 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Optical Activity | NONE |
Istradefylline is a first-in-class adenosine A2A receptor antagonist antiparkinsonian agent and has been marketed as the brand name NOURIAST® in Japan since May 30, 2013. NOURIAST is indicated for the improvement of wearing-off phenomena in patients with Parkinson’s disease on concomitant treatment
with levodopa-containing products.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL251 |
12.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | NOURIAST Approved UseImprovement of wearing-off phenomena in patients with Parkinson’s disease on concomitant treatment
with levodopa-containing products. Launch Date2013 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
230.9 ng/mL |
20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ISTRADEFYLLINE unknown | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3249 ng × h/mL |
20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ISTRADEFYLLINE unknown | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
72.1 h |
20 mg 1 times / day steady-state, oral dose: 20 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ISTRADEFYLLINE unknown | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: |
unhealthy, 65 years (range: 33 - 84 years) n = 124 Health Status: unhealthy Age Group: 65 years (range: 33 - 84 years) Sex: M+F Population Size: 124 Sources: |
Disc. AE: Dyskinesia... AEs leading to discontinuation/dose reduction: Dyskinesia (6%) Sources: |
120 mg 1 times / day steady, oral Highest studied dose Dose: 120 mg, 1 times / day Route: oral Route: steady Dose: 120 mg, 1 times / day Sources: Page: p. 53 |
unhealthy n = 142 Health Status: unhealthy Population Size: 142 Sources: Page: p. 53 |
Other AEs: Chest pain... Other AEs: Chest pain (0.7%) Sources: Page: p. 53 |
300 mg single, oral Highest studied dose Dose: 300 mg Route: oral Route: single Dose: 300 mg Sources: Page: p. 16 |
unhealthy Health Status: unhealthy Condition: Parkinson’s disease Sources: Page: p. 16 |
|
120 mg single, oral Overdose Dose: 120 mg Route: oral Route: single Dose: 120 mg Sources: |
unhealthy n = 1 Health Status: unhealthy Population Size: 1 Sources: |
Other AEs: Hallucinations, Agitation... Other AEs: Hallucinations Sources: Agitation Dyskinesia |
40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: Page: p. 38 |
unhealthy n = 378 Health Status: unhealthy Population Size: 378 Sources: Page: p. 38 |
Disc. AE: Visual hallucinations, Hallucination olfactory... Other AEs: Auditory hallucinations... AEs leading to discontinuation/dose reduction: Visual hallucinations (1%) Other AEs:Hallucination olfactory (1%) Somatic hallucination (1%) Auditory hallucinations (1%) Sources: Page: p. 38 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Dyskinesia | 6% Disc. AE |
40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: |
unhealthy, 65 years (range: 33 - 84 years) n = 124 Health Status: unhealthy Age Group: 65 years (range: 33 - 84 years) Sex: M+F Population Size: 124 Sources: |
Chest pain | 0.7% | 120 mg 1 times / day steady, oral Highest studied dose Dose: 120 mg, 1 times / day Route: oral Route: steady Dose: 120 mg, 1 times / day Sources: Page: p. 53 |
unhealthy n = 142 Health Status: unhealthy Population Size: 142 Sources: Page: p. 53 |
Agitation | 120 mg single, oral Overdose Dose: 120 mg Route: oral Route: single Dose: 120 mg Sources: |
unhealthy n = 1 Health Status: unhealthy Population Size: 1 Sources: |
|
Dyskinesia | 120 mg single, oral Overdose Dose: 120 mg Route: oral Route: single Dose: 120 mg Sources: |
unhealthy n = 1 Health Status: unhealthy Population Size: 1 Sources: |
|
Hallucinations | 120 mg single, oral Overdose Dose: 120 mg Route: oral Route: single Dose: 120 mg Sources: |
unhealthy n = 1 Health Status: unhealthy Population Size: 1 Sources: |
|
Auditory hallucinations | 1% | 40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: Page: p. 38 |
unhealthy n = 378 Health Status: unhealthy Population Size: 378 Sources: Page: p. 38 |
Hallucination olfactory | 1% Disc. AE |
40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: Page: p. 38 |
unhealthy n = 378 Health Status: unhealthy Population Size: 378 Sources: Page: p. 38 |
Somatic hallucination | 1% Disc. AE |
40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: Page: p. 38 |
unhealthy n = 378 Health Status: unhealthy Population Size: 378 Sources: Page: p. 38 |
Visual hallucinations | 1% Disc. AE |
40 mg 1 times / day steady, oral Recommended Dose: 40 mg, 1 times / day Route: oral Route: steady Dose: 40 mg, 1 times / day Sources: Page: p. 38 |
unhealthy n = 378 Health Status: unhealthy Population Size: 378 Sources: Page: p. 38 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Drug as victim
PubMed
Title | Date | PubMed |
---|---|---|
Cellular and behavioural effects of the adenosine A2a receptor antagonist KW-6002 in a rat model of l-DOPA-induced dyskinesia. | 2003 Mar |
|
Forebrain adenosine A2A receptors contribute to L-3,4-dihydroxyphenylalanine-induced dyskinesia in hemiparkinsonian mice. | 2006 Dec 27 |
|
2,6,8-trisubstituted 1-deazapurines as adenosine receptor antagonists. | 2007 Feb 22 |
|
Tremorolytic effects of adenosine A2A antagonists: implications for parkinsonism. | 2008 May 1 |
|
The effects of adenosine A2A receptor antagonists on haloperidol-induced movement disorders in primates. | 2008 Oct |
|
Dual inhibition of monoamine oxidase B and antagonism of the adenosine A(2A) receptor by (E,E)-8-(4-phenylbutadien-1-yl)caffeine analogues. | 2008 Sep 15 |
|
Effects of the adenosine A 2A antagonist KW 6002 (istradefylline) on pimozide-induced oral tremor and striatal c-Fos expression: comparisons with the muscarinic antagonist tropicamide. | 2009 Sep 29 |
|
Discovery of phosphoric acid mono-{2-[(E/Z)-4-(3,3-dimethyl-butyrylamino)-3,5-difluoro-benzoylimino]-thiazol-3-ylmethyl} ester (Lu AA47070): a phosphonooxymethylene prodrug of a potent and selective hA(2A) receptor antagonist. | 2011 Feb 10 |
|
International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and classification of adenosine receptors--an update. | 2011 Mar |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: http://www.e-search.ne.jp/~jpr/PDF/KYOWA13.PDF
To be administered concomitantly with levodopa-containing products.
The usual adult dosage of istradefylline is 20 mg orally administered once daily. According to
symptoms, 40 mg of istradefylline can be orally administered once daily.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23812646
The binding kinetics of istradefylline to the human A2A receptor
were investigated using 1 nmol/L of [3H]-istradefylline binding to the human A2A receptor.
Substance Class |
Chemical
Created
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admin
on
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Sat Dec 16 17:52:37 GMT 2023
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admin
on
Sat Dec 16 17:52:37 GMT 2023
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Record UNII |
2GZ0LIK7T4
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C38149
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m6559
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PRIMARY | Merck Index | ||
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NOURIAST
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PRIMARY | APPROVED MARCH 2013 | ||
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5311037
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2199015
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8387
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DB11757
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CHEMBL431770
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155270-99-8
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2GZ0LIK7T4
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DTXSID7057652
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ISTRADEFYLLINE
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2GZ0LIK7T4
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C111599
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C73268
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100000152133
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OO-61
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5608
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Related Record | Type | Details | ||
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
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TARGET->WEAK INHIBITOR |
Ki
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||
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
|
||
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BINDER->LIGAND |
BINDING
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METABOLIC ENZYME -> SUBSTRATE |
MAJOR
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||
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
|
||
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EXCRETED UNCHANGED |
AMOUNT ADMINISTERED
FECAL
|
||
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TARGET->WEAK INHIBITOR |
Ki
|
||
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METABOLIC ENZYME -> SUBSTRATE |
MINOR
|
Related Record | Type | Details | ||
---|---|---|---|---|
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METABOLITE -> PARENT |
FECAL
|
||
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METABOLITE -> PARENT |
FECAL
|
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METABOLITE -> PARENT |
FECAL
|
||
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METABOLITE -> PARENT |
PLASMA; URINE
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METABOLITE -> PARENT |
FECAL
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METABOLITE -> PARENT |
PLASMA
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METABOLITE -> PARENT |
FECAL
|
||
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METABOLITE -> PARENT |
PLASMA
|
Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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Tmax | PHARMACOKINETIC |
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ORAL ADMINISTRATION |
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Biological Half-life | PHARMACOKINETIC |
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