Preladenant

A potent and highly selective A2A receptor competitive antagonist with Ki of 1.1 nM; has >1000-fold selectivity over all other adenosine receptors; attenuates hypolocomotion induced by the A2AR agonist CGS-21680; potentiates L-Dopa -induced contralateral rotations after 6-hydroxydopamine lesions in the medial forebrain bundle in rats (0.1-1 mg/kg) ; orally active. (In Vitro) :Preladenant also completely antagonizes cAMP in cells expressing the recombinant human A2A receptor. Preladenant is determined to has KB values of 1.3 nM at the A2A receptor; the value is in good agreement with the Ki value determined in the radioligand binding assay. A similar functional assay with A2B receptor-expressing cells is used to demonstrate selectivity over A2B receptors. In this assay, the KB value for Preladenant is 1.2 μM, indicating that Preladenant is 923-fold selective for the A2A receptor over the A2B receptor. (In Vivo) :Preladenant (1 mg/kg) inhibits L-Dopa-induced behavioral sensitization after repeated daily administration, which suggests a reduced risk of the development of dyskinesias. Preladenant exhibits antidepressant-like profiles in models of behavioral despair, namely the mouse tail suspension test and the mouse and rat forced swim test. Preladenant produces a dose-dependent reduction in parkinsonian scores at doses of 1 mg/kg (min score: 9.0) and 3 mg/kg (min score: 6.5) . A subthreshold dose of Preladenant reduces minimum and mean parkinsonian scores in animals treated with 3 mg kg of L-Dopa to 5.25 and 6.88 respectively. A Wilcoxin test is used to compare individual treatments against vehicle. Preladenant (3 mg/kg), L-Dopa (3, 6, and 12 mg/kg), and the combination of Preladenant and L-Dopa (1 or 3 mg/kg+3 mg/kg) are all significantly improved on the minimum parkinsonian score. In addition, both the 12 mg/kg L-Dopa and L-Dopa+Preladenant groups are significantly improved on both minimum and mean parkinsonian scores relative to the 3 mg/kg L-Dopa group.

377727-87-2

SCH-420814 | SCH 420814 | SCH420814

>98% (HPLC)

DMSO

NC1=NC (N (CCN2CCN (C3=CC=C (OCCOC) C=C3) CC2) N=C4) =C4C5=NC (C6=CC=CO6) =NN15

C25H29N9O3

503.5563

Storage temperature: -20°C. Stability: ≥ 2 years

For research use only.