A-33 (A33) is a potent and selective catalytic site-targeting PDE4B inhibitor (IC50 = 15 nM/PDE4B vs. 1.7 μM/PDE4D) that effectively prevents PDE4B-medicated cellular cAMP hydrolysis (150%/320% increased cAMP level with 100 nM/1 μM A-33 pre-treament in murine hippocampal HT-22 cells following 10 nM isoproterenol stimulation) in vitro and inhibits LPS-induced TNF-α production in mice in vivo (ID50 = 14 mg/kg p.o.). When administered via intraperitoneal injection, A-33 improves cognitive function in a rat model of traumatic brain injury (0.3 mg/kg i.p.) and exhibits antidepressant property in mice (0.3-1 mg/kg i.p.) in vivo.
