product name Istradefylline
Description: Istradefylline (also known as KW-6002) is a potent and selective adenosine A2A receptor (A2AR) antagonist with Ki of 2.2 nM. It has been found to be useful in the treatment of Parkinsons disease. The affinity of KW-6002 for the A2AR is 70-fold greater than that for the A1 receptor. The binding affinities (Ki) of KW-6002 for human A1 receptor and A2A receptor are >287 nM and 9.12 nM, respectively. Istradefylline reduces dyskinesia resulting from long-term treatment with classical antiparkinson drugs such as levodopa. Istradefylline is an analog of caffeine.
References: J Neurosci. 2001 May 15;21(10):RC143; Psychopharmacology (Berl). 1999 Nov;147(1):90-5.
384.43
Formula
C20H24N4O4
CAS No.
155270-99-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 6 mg/mL (15.6 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
30% Propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL
Synonyms
KW-6002
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19394035
| In Vitro |
In vitro activity: The affinity of Istradefylline for the A2AR is 70-fold greater than that for the A1 receptor with Ki of 2.2 nM versus 150 NM. Exposure of primary rat striatal astrocytes to Istradefylline results in concentration-dependent abolition of bFGF induction of astrogliosis in vitro. Binding affinities (Ki) of Istradefylline for A1 receptor, A2A receptor, and A3 receptor in human are >287 nM, 9.12 nM, and >681 nM, respectively, for A1 receptor and A2A receptor in rat 50.9 nM and 1.57 nM, respectively, and for A1 receptor and A2A receptor in mouse 105.02 nM and 1.87 nM, respectively. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | Istradefylline reverses CGS21680-induced and reserpine-induced catalepsy with ED50 of 0.05 mg/kg and 0.26 mg/kg, respectively. Istradefylline is over 10 times as potent in these models compared to other adenosine antagonists and dopamine agonist drugs. Administration of Istradefylline in combination with L-dopa (50 mg/kg) exerts prominent effects on haloperidol-induced and reserpine-induced catalepsy. Oral administration of Istradefylline at 10 mg/kg to MPTP-treated common marmosets produces an increase in locomotor activity to approximately twice that of control and improves motor disability. Administration of Istradefylline (10 mg/kg, po, 90 minutes before SKF80723/quinpirole/L-DOPA) in combination with SKF80723 (1 mg/kg, ip), quinpirole (0.06 mg/kg ip), or L-DOPA (2.5 mg/kg po) produces a significant additive effect on locomotor activity and improvement of motor disability but not dyskinesia. In the MPTP mice model, Istradefylline significantly attenuates striatal dopamine depletion under various conditions. Pretreatment with Istradefylline (3.3 mg/kg, i.p.) before a single dose of MPTP attenuates the partial dopamine and DOPAC depletions measured in striata 1 week later. Oral administration of Istradefylline protects against the loss of nigral dopaminergic neuronal cells induced by 6-hydroxydopamine in rats, and prevents the functional loss of dopaminergic nerve terminals in the striatum and the ensuing gliosis caused by MPTP in mice. Chronic Istradefylline treatment does not improve the reversal deficits in dopamine-depleted rats. The tremulous jaw movements induced by pimozide are significantly reduced by co-administration of either Istradefylline or tropicamide. Pimozide-induced increases in ventrolateral striatal c-Fos expression are reduced by a behaviorally effective dose of Istradefylline, in contrast to tropicamide by which c-Fos expression in pimozide-treated rats is actually increased. |
| Animal model | Common marmosets (Callithrix jacchus) with MPTP treatment |
| Formulation & Dosage | Suspended in 0.3% Tween-80 and 10% sucrose solution; 10 mg/kg; p.o. |
| References | J Neurosci. 2001 May 15;21(10):RC143; Psychopharmacology (Berl). 1999 Nov;147(1):90-5. |
Related Posts
product name Istradefylline
Description: Istradefylline (also known as KW-6002) is a potent and selective adenosine A2A receptor (A2AR) antagonist with Ki of 2.2 nM. It has been found to be useful in the treatment of Parkinsons disease. The affinity of KW-6002 for the A2AR is 70-fold greater than that for the A1 receptor. The binding affinities (Ki) of KW-6002 for human A1 receptor and A2A receptor are >287 nM and 9.12 nM, respectively. Istradefylline reduces dyskinesia resulting from long-term treatment with classical antiparkinson drugs such as levodopa. Istradefylline is an analog of caffeine.
References: J Neurosci. 2001 May 15;21(10):RC143; Psychopharmacology (Berl). 1999 Nov;147(1):90-5.
384.43
Formula
C20H24N4O4
CAS No.
155270-99-8
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 6 mg/mL (15.6 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
30% Propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL
Synonyms
KW-6002
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19394035
| In Vitro |
In vitro activity: The affinity of Istradefylline for the A2AR is 70-fold greater than that for the A1 receptor with Ki of 2.2 nM versus 150 NM. Exposure of primary rat striatal astrocytes to Istradefylline results in concentration-dependent abolition of bFGF induction of astrogliosis in vitro. Binding affinities (Ki) of Istradefylline for A1 receptor, A2A receptor, and A3 receptor in human are >287 nM, 9.12 nM, and >681 nM, respectively, for A1 receptor and A2A receptor in rat 50.9 nM and 1.57 nM, respectively, and for A1 receptor and A2A receptor in mouse 105.02 nM and 1.87 nM, respectively. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | Istradefylline reverses CGS21680-induced and reserpine-induced catalepsy with ED50 of 0.05 mg/kg and 0.26 mg/kg, respectively. Istradefylline is over 10 times as potent in these models compared to other adenosine antagonists and dopamine agonist drugs. Administration of Istradefylline in combination with L-dopa (50 mg/kg) exerts prominent effects on haloperidol-induced and reserpine-induced catalepsy. Oral administration of Istradefylline at 10 mg/kg to MPTP-treated common marmosets produces an increase in locomotor activity to approximately twice that of control and improves motor disability. Administration of Istradefylline (10 mg/kg, po, 90 minutes before SKF80723/quinpirole/L-DOPA) in combination with SKF80723 (1 mg/kg, ip), quinpirole (0.06 mg/kg ip), or L-DOPA (2.5 mg/kg po) produces a significant additive effect on locomotor activity and improvement of motor disability but not dyskinesia. In the MPTP mice model, Istradefylline significantly attenuates striatal dopamine depletion under various conditions. Pretreatment with Istradefylline (3.3 mg/kg, i.p.) before a single dose of MPTP attenuates the partial dopamine and DOPAC depletions measured in striata 1 week later. Oral administration of Istradefylline protects against the loss of nigral dopaminergic neuronal cells induced by 6-hydroxydopamine in rats, and prevents the functional loss of dopaminergic nerve terminals in the striatum and the ensuing gliosis caused by MPTP in mice. Chronic Istradefylline treatment does not improve the reversal deficits in dopamine-depleted rats. The tremulous jaw movements induced by pimozide are significantly reduced by co-administration of either Istradefylline or tropicamide. Pimozide-induced increases in ventrolateral striatal c-Fos expression are reduced by a behaviorally effective dose of Istradefylline, in contrast to tropicamide by which c-Fos expression in pimozide-treated rats is actually increased. |
| Animal model | Common marmosets (Callithrix jacchus) with MPTP treatment |
| Formulation & Dosage | Suspended in 0.3% Tween-80 and 10% sucrose solution; 10 mg/kg; p.o. |
| References | J Neurosci. 2001 May 15;21(10):RC143; Psychopharmacology (Berl). 1999 Nov;147(1):90-5. |