Background:

Bromisoval has anti-inflammatory effects and has been used as an old sedative and hypnotic.

Bromisoval (BU) suppresses nitric oxide (NO) releasing and proinflammatory cytokine expression in lipopolysaccharide (LPS)-treat BV2 cells, a murine microglial cell line. Bromisoval suppresses LPS-inducing phosphorylation of signal transducer and activator of transcription 1 (STAT1) and expression of interferon regulatory factor 1 (IRF1). The Janus kinase 1 (JAK1) inhibitor filgotinib suppresses the NO release much more weakly than that of Bromisoval, although filgotinib almost completely prevents LPS-inducing STAT1 phosphorylation. Knockdown of JAK1, STAT1, or IRF1 does not affect the suppressive effects of Bromisoval on LPS-inducing NO. A combination of Bromisoval and filgotinib synergistically suppress the NO releasing. The mitochondrial complex I inhibitor rotenone, which does not prevent STAT1 phosphorylation or IRF1 expression, suppresses proinflammatory mediator expression less significantly than Bromisoval. Bromisoval and rotenone reduce intracellular ATP (iATP) levels to a similar extent. A combination of rotenone and filgotinib suppress NO release in LPS-treated BV2 cells as strongly as Bromisoval[1].

Bromisoval (Bromvaletone) and carbromal are the most potent central depressants within each series. Depressant activities (ISD50 values) and acute toxicities (LD50 values) in male mice after intraperitoneal injection of Bromisoval are 0.35 (0.30-0.39) and 3.25 (2.89-3.62) mmol/kg, respectively[2].

[1]. Kawasaki S, et al. Effects of hypnotic bromovalerylurea on microglial BV2 cells. J Pharmacol Sci. 2017 Jun;134(2):116-123. [2]. Mrongovius RI, et al. Comparison of the bromureide sedative-hypnotic drugs, bromvaletone (bromisoval) and carbromal, and their chloro analogues in mice. Clin Exp Pharmacol Physiol. 1976 Sep-Oct;3(5):443-7.