PSB 0777 ammonium drate is a potent and selective adenosine A2A receptor full agonist with Ki values of 44.4 nM, 360 nM for rat and human A2A receptors, respectively. PSB 0777 ammonium drate has Ki values of ≥10000 nM, 541 nM for rat and human A1 receptors, respectively. PSB 0777 ammonium drate shows poor brain penetrant and perorally non-absorbable effect. PSB 0777 ammonium drate has the potential for inflammatory bowel disease (IBS) research research.
PSB 0777 ammonium drate (compound 7) shows high selectivity for the A2AAR (>225-fold) versus the other AR subtypes (Ki values of >10000 nM and ≫10000 for human A2B receptor and A3 receptor, respectively). PSB 0777 ammonium drate acts as an full agonist at A2AAR with an EC50 value of 117 nM in CHO-K1 cells[1]. PSB-0777 ammonium binds human β1 (Ki=4.4 μM) and β3 (Ki=3.3 μM) adrenergic receptors[2]. PSB 0777 ammonium drate (0.1 µM, 1 µM, 10 µM) increases concentration-dependently Acetylcholine (Ach, 1 mM) contractions in untreated and inflamed rat ileum/jejunum preparations in ex vivo experiments[1].
PSB 0777 ammonium drate (0.4 mg/kg/day; oral gavage; from the day 5 to 10) causes a marked reduction of inflammatory cell infiltration and an amelioration of colonic mucosal architecture[3]. PSB 0777 ammonium drate (0.03, 0.3, 3 mg/kg; i.p.) causes dose-dependent pothermia and poactivity in C57BL/6J mice[2]. PSB 0777 ammonium drate cannot be absorbed systemically by the digestive mucosa once administered by the oral route. PSB 0777 ammonium drate (0.4 mg/kg/day; PO) has very low plasma concentrations in rats at 30 min (below 5 nM), and there is no plasma concentrations at 60 min after administration. PSB 0777 ammonium drate (0.4 mg/kg/day; IP) makes plasma concentrations well evident at 30 min, and decreases after 60 min, and is not detectable at 120 and 240 min[3].
References:
[1]. Ali El-Tayeb, et al. Development of Polar Adenosine A2A Receptor Agonists for Inflammatory Bowel Disease: Synergism with A2B Antagonists. ACS Med Chem Lett. 2011 Oct 10;2(12):890-5.
[2]. Jesse Lea Carlin, et al.Activation of adenosine A 2A or A 2B receptors causes pothermia in mice. Neuropharmacology. 2018 Sep 1;139:268-278.
[3]. L Antonioli, et al. Anti-inflammatory effect of a novel locally acting A 2A receptor agonist in a rat model of oxazolone-induced colitis. Purinergic Signal. 2018 Mar;14(1):27-36.