Novel antioxidant(3)：Pharmacological profiles of A-3877, a new drug for acute stroke

A-3877 (4- (±) - (5-amino-2, 4, 6, 7-tetramethyldihydrobenzo furan - 2-ylmethyl) aminophenyl-5-pyrazole) were investigated on 1) inhibition of lipid peroxidation in rat brain homogenates by FeCl2 in vitro, and in rats (100mg/kg, i. p. ) ex vivo, 2) in vivo antioxidative effect on injury by intrathec...

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Published in:Journal of Pharmacological Sciences 2004, Vol.94 (suppl.3), p.293-293
Main Authors: Yasuyuki Shiinoki, Seiichi Uchida, Seiichi Ikeyama, Hiroko Moroe, Chizuru Hichiya, Nobuhiro Umeda, Mitsumasa Takata, Shirou Tsubokura, Fumie Shirato, Nobuo Mochizuki
Format: Article
Language:Japanese
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Summary:A-3877 (4- (±) - (5-amino-2, 4, 6, 7-tetramethyldihydrobenzo furan - 2-ylmethyl) aminophenyl-5-pyrazole) were investigated on 1) inhibition of lipid peroxidation in rat brain homogenates by FeCl2 in vitro, and in rats (100mg/kg, i. p. ) ex vivo, 2) in vivo antioxidative effect on injury by intrathecal injection of FeCl2 in mice, 3) in vivo protective effect on brain edema by a middle cerebral artery occlusion ischemia (2hr) -reperfusion (24hr) model (MCAO) in rats. [Results] 1) IC50 were 0.42μM (A-3877) and 29μM (edaravone) in vitro. The high inhibition of A-3877 (96%) on ex vivo showed good permeability of blood-brain barrier. 2) ID50 of A-3788 on a behavioral responses in vivo were 16mg/kg, i. p. , and 17 mg/kg, p. o. 4) The injection of A-3877 (0.1mg/kg, i. v. ) and edaravone (3mg/kg, i. v. ) just after the reperfusion improved the brain edema (37% and 25%, respectively). Safety range of A-3877 (LD50/effective dose of MCAO) was over 1000 times. Therefore, A-3877 is an attractive candidate for the treatment of acute stroke.
ISSN:1347-8613