BRL 44408 Maleate is a potent α2A-adrenoceptor antagonist with antidepressant and analgesic activity that reduces lipopolysaccharide (LPS)-induced expression and attenuates endogenous lipopolysaccharide-induced acute lung injury through inhibition of the mitogen-activated protein kinase kinase/extracellularly regulated protein kinase signaling pathway in mice.

α2A-adrenoceptor:8.5 nM (Ki), α2A-adrenoceptor:7.9 nM (K (B))

BRL 44408 Maleate Salt, a potent (Ki=8.5 nM) and selective (>50-fold) alpha2A-adrenoceptor antagonist (K(B)=7.9 nM). [1]

In rats, BRL 44408 Maleate Salt penetrated the central nervous system resulting in peak brain and plasma concentrations of 586 ng/g and 1124 ng/ml, respectively. In a pharmacodynamic assay, pretreatment with BRL 44408 Maleate Salt to rats responding under a fixed-ratio 30 operant response paradigm resulted in a rightward shift of the clonidine dose-response curve, an effect indicative of alpha2-adrenoceptor antagonism in vivo. [1]