Imisopasem manganese (M40403) is a manganese superoxide MnSOD non-peptidyl mimetic.

M40403 removes superoxide anions without interfering with other reactive species known to be involved in inflammatory responses (e.g. nitric oxide, NO and peroxynitrite)[1].

M40403 has shown efficacy in animal model disease states in which superoxide anions are thought to play a key role. M40403 inhibits the inflammatory response following the intrapleural injection of carrageenan in rats. All parameters of inflammation are attenuated by M40403 except for NOx, PGE2 and IL-10 which remains unaltered [1]. Decreased apoptosis of the large and particularly the small bowel and marked recovery of both lymphoid and hematopoietic tissues occurs in the M40403 pre-treated mice [2].

Rats: Male Sprague-Dawley rats are used in the study. M40403 (5-20?mg?kg-1), or an equivalent volume (0.3?mL) of the vehicle (26?mm sodium bicarbonate buffer, pH?8.1-8.3), is injected intraperitoneally (i.p.) 15?min before carrageenan. At 4?h after the injection of carrageenan, the animals are killed by inhalation of CO2 [1]. Mice: 30 mg dry powder M40403 is dissolved in 6.0 ml SBC adjusted to pH 8.3 with 1 M NaOH. This stock solution is diluted to 1.25 mg/mL in SBC. Two experimental models are tested. In one, the dose of IR is held constant at 8.5 Gy total body irradiation (TBI). The mice are injected i.p. with a single dose of 40 mg/kg, 30 mg/kg, 20 mg/kg or 10 mg/kg M40403. Thirty minutes later the mice receive 8.5 Gy total body irradiation (TBI). Control animals received 0.1 ml of SBC buffer prior to TBI. In the other model, groups of 20 mice receive either 6.5 or 7.5 Gy TBI. One half of each group is treated with 2.0 mg/kg M40403 i.p. and the other with SBC 30 min before TBI [2].