EVALUATION OF NEFOPAM AS A MONOAMINE UPTAKE INHIBITOR IN-VIVO IN MICE

被引:64
作者
FULLER, RW
SNODDY, HD
机构
[1] Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis
关键词
NEFOPAM; SEROTONIN; NOREPINEPHRINE; 5-HYDROXYINDOLEACETIC ACID; P-CHLORAMPHETAMINE; 6-HYDROXYDOPAMINE;
D O I
10.1016/0028-3908(93)90064-A
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Nefopam antagonized 6-hydroxydopamine-induced depletion of heart norepinephrine in mice with an ED50 value of 12 mg/kg. Nefopam was ineffective in antagonizing p-chloroamphetamine-induced depletion of brain serotonin in our standard assay in mice, apparently due to a short duration of action. Brain concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) were decreased after a 32 mg/kg, i.p., dose of nefopam at 1 and 2 hr but not at 4 hT. When nefopam was injected simultaneously with p-chloroamphetamine, it prevented brain serotonin depletion initially, but by 6 hr the protective effect was essentially lost, suggesting that p-chloroamphetamine persisted in mouse brain longer than did nefopam. Nefopam caused a dose-related antagonism of brain serotonin depletion at 2 hr after injection of a low dose of p-chloroamphetamine hydrochloride (10 mg/kg, i.p.), with a calculated ED50 value of 11 mg/kg. The lowering of brain 5-HIAA concentration 2 hr after nefopam injection occurred after a 32 mg/kg dose but not after a 3 or 10 mg/kg dose. These data suggest that nefopam is effective as an inhibitor of norepinephrine and serotonin uptake at doses previously shown to be analgesic in mice, consistent with uptake inhibition being a postulated mechanism important in its analgesic effect. Nonetheless, nefopam is a relatively weak inhibitor of monoamine uptake with a short duration of action in mice.
引用
收藏
页码:995 / 999
页数:5
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