Ibudilast

PDE4抑制剂（PDE4A-D的IC50s分别为54、65、239和166nM）；对PDE4的选择性优于PDE1、PDE7A、PDE7B和PDE9A（所有化合物的IC50均为≥10,000nM），但抑制PDE3A、PDE3B和PDE5A（IC50分别为1,600、2,700和3,510nM）；在分离的人全血中抑制LPS诱导的TNF-α产生和fMLP诱导的LTB4产生（IC50分别为6.2和2.5μM）；在5mg/kg剂量下，可抑制白三烯介导的过敏性支气管痉挛豚鼠模型中34%的支气管痉挛；防止MPTP诱发的帕金森病小鼠模型中纹状体中TNF-α、IL-1β和IL-6表达的增加；每天两次分别以40和50mg/kg的剂量增加接受MPTP治疗和未接受MPTP治疗的小鼠纹状体中GDNF的表达。An inhibitor of PDE4 (IC50s = 54, 65, 239, and 166 nM for PDE4A-D, respectively); selective for PDE4 over PDE1, PDE7A, PDE7B, and PDE9A (IC50 = ≥10,000 nM for all) but does inhibit PDE3A, PDE3B, and PDE5A (IC50s = 1,600, 2,700, and 3,510 nM, respectively); inhibits LPS-induced production of TNF-α and fMLP-induced production of LTB4 in isolated human whole blood (IC50s = 6.2 and 2.5 μM, respectively); inhibits bronchospasm by 34% in a guinea pig model of leukotriene-mediated allergic bronchospasm at 5 mg/kg; prevents increases in TNF-α, IL-1β, and IL-6 expression in the striatum in a mouse model of MPTP-induced Parkinson's disease; increases striatal expression of GDNF in MPTP-treated and -untreated mice when at 40 and 50 mg/kg, respectively, twice per day.