ASP5854

ASP5854 is an orally active, blood-brain barrier permeable adenosine A1/A2a dual receptor antagonist. ASP5854 blocks receptor activity and agonist-induced intracellular calcium elevation, and exhibits the characteristic of slow dissociation from striatal A2a receptors in primates. ASP5854 reverses catalepsy, enhances cognitive ability, improves motor function and exerts neuroprotective effects, while also alleviating dyskinesia and increasing contralateral turning behavior. ASP5854 is mainly used in studies related to ischemic stroke and Parkinson's disease^[1][2][3][4]. In Vitro:ASP5854 (various concentrations; 60 min) potently and selectively binds to human, rat, and mouse adenosine A₁ and A_2a receptors, with K_i values ranging from 1.24 to 12.48 nM, and exhibits no significant affinity for A₃ receptors^[2].
ASP5854 displays dual A₂A/A₁ AR binding affinity with a K_i of 1.76 nM at human A₂A AR and 9.03 nM at human A₁ AR^[1].
ASP5854 (various concentrations; 10 s) acts as a potent functional antagonist of human adenosine A₁ and A_2a receptors in transfected CHO cells, inhibiting agonist-induced intracellular Ca²⁺ elevation with IC₅₀ values of 59.81 nM and 4.21 nM, respectively^[2]. In Vivo:ASP5854 (0.01-3.2 mg/kg; p.o.; single dose) dose-dependently reverses CGS21680-induced catalepsy in mice with an ED₅₀ of 0.147 mg/kg, showing significant efficacy at doses ≥0.32 mg/kg^[2].
ASP5854 (0.01-3.2 mg/kg; p.o.; single dose) dose-dependently reverses haloperidol-induced catalepsy in mice with an ED₅₀ of 0.066 mg/kg, showing significant efficacy at doses ≥0.1 mg/kg^[2].
ASP5854 (0.01-1 mg/kg; p.o.; single dose) reduces haloperidol-induced cataleptic duration in rats, with significant efficacy starting at a dose of 0.1 mg/kg^[2].
ASP5854 (0.01-1 mg/kg; p.o.; single dose) significantly potentiates L-DOPA-induced contralateral turning behavior in 6-hydroxydopamine-lesioned hemiparkinsonian rats at doses of 0.032 to 1 mg/kg^[2].
ASP5854 (0.032-3.2 mg/kg; p.o.; single dose) reverses scopolamine-induced spontaneous alternation deficits in the mouse Y-maze test, showing significant efficacy at doses of 0.32 and 1 mg/kg^[2].
ASP5854 (0.032-1 mg/kg; p.o.; single dose) reverses MK-801-induced spontaneous alternation deficits in the mouse Y-maze test, showing significant efficacy at doses of 0.32 and 1 mg/kg^[2].