Istradefylline | CAS:155270-99-8

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Name:Istradefylline; KW-6002
Cat. No. :CS-0737
CAS No. :155270-99-8
Formula:C20H24N4O4
M. Wt. : 384.43
Solubility:DMSO:

Istradefylline is a very potent, selective and orally active adenosine A2A receptor antagonist with Ki of 2.2 nM in experimental models of Parkinson's disease.IC50 & Target: Ki: 2.2 nM (adenosine A2A receptor)In Vitro: 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[1]. Exposure of primary rat striatal astrocytes to Istradefylline results in concentration-dependent abolition of bFGF induction of astrogliosis in vitro[4]. 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[5]. In Vivo: 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[1]. 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[2]. 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, p.o., 90 minutes before SKF80723/quinpirole/L-DOPA) in combination with SKF80723 (1 mg/kg, i.p.), quinpirole (0.06 mg/kg i.p.), or L-DOPA (2.5 mg/kg p.o.) produces a significant additive effect on locomotor activity and improvement of motor disability but not dysKinesia[3].

Brambilla R, et al. Blockade of A2A adenosine receptors prevents basic fibroblast growth factor-induced reactive astrogliosis in rat striatal primary astrocytes. Glia. 2003 Aug;43(2):190-4. Chen JF, et al. Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model of Parkinson's disease. J Neurosci. 2001 May 15;21(10):RC143. Mihara T, et al. Pharmacological characterization of a novel, potent adenosine A1 and A2A receptor dual antagonist, 5-[5-amino-3-(4-fluorophenyl)pyrazin-2-yl]-1-isopropylpyridine-2(1H)-one (ASP5854), in models of Parkinson's disease and cognition. J Pharm Shiozaki S, et al. Actions of adenosine A2A receptor antagonist KW-6002 on drug-induced catalepsy and hypokinesia caused by reserpine or MPTP. Psychopharmacology (Berl). 1999 Nov;147(1):90-5. Kanda T, et al. Combined use of the adenosine A(2A) antagonist KW-6002 with L-DOPA or with selective D1 or D2 dopamine agonists increases antiparkinsonian activity but not dyskinesia in MPTP-treated monkeys. Exp Neurol. 2000 Apr;162(2):321-7.