| ironjustice@aol.com 2005-08-18, 5:55 pm |
| It seems the .. mode of action .. OF .. this .. drug .. may be .. IRON
... based .. ?
<<snip>>
MCI-186 inhibited iron-dependent peroxidation in rat brain homogenates
and mitochondrial homogenates and prevented iron-dependent peroxidative
disintegration of mitochondrial membranes .
<<snip>>
1: J Pharmacol Exp Ther. 1994 Mar;268(3):1597-604. Related Articles,
Links
Protective effects of MCI-186 on cerebral ischemia: possible
involvement of free radical scavenging and antioxidant actions.
Watanabe T, Yuki S, Egawa M, Nishi H.
Pharmaceuticals Laboratory I, Mitsubishi Kasei Corporation, Yokohama,
Japan.
The anti-ischemic effects and a possible mechanism of a new antistroke
agent, 3-methyl-1-phenyl-pyrazolin-5-one (MCI-186), were studied.
Preischemic treatment with MCI-186 (3 mg/kg i.v.) facilitated the
recovery of electrocorticographic activity and prolonged survival time
in global complete ischemia of rats; MCI-186 (1 and 3 mg/kg i.v.) also
mitigated dysfunction of the blood-brain barrier and energy failure in
hemispheric embolization of rats. Postischemic treatment with MCI-186
(3 mg/kg i.v.) decreased cortical infarction in focal embolization of
rats. MCI-186 (0.6-2.4 mM) inhibited the OH.-induced hydroxylation of
salicylate (maximal inhibition, 40.2%), but at 100 microM it did not
influence O2- generation. MCI-186 inhibited the formation of linoleic
acid-conjugated dienes caused by OH. (IC50 = 32.0 microM). Also,
concurrent administration of MCI-186 (3-100 mg/kg i.v.) ameliorated
hyperglycemia, hyperlipopeoxidemia and degranulation of beta-cells in
alloxan (40 mg/kg i.v.)-treated rats. In addition, MCI-186 inhibited
iron-dependent peroxidation in rat brain homogenates and mitochondrial
homogenates (IC50 = 15.0 and 2.3 microM, respectively) and prevented
iron-dependent peroxidative disintegration of mitochondrial membranes
(IC50 = 39.0 microM). These findings suggest that MCI-186 has potent
anti-ischemic actions and that its mechanism may be closely associated
with beneficial antioxidant activities.
PMID: 8138971 [PubMed - indexed for MEDLINE]
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