Evaluation of nefopam as a monoamine uptake inhibitor in vivo in mice

Neuropharmacology. 1993 Oct;32(10):995-9. doi: 10.1016/0028-3908(93)90064-a.

Abstract

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 hr. 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.

MeSH terms

  • Animals
  • Biogenic Monoamines / metabolism*
  • Brain Chemistry / drug effects
  • Dose-Response Relationship, Drug
  • Hydroxyindoleacetic Acid / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Myocardium / metabolism
  • Nefopam / pharmacology*
  • Neurotransmitter Uptake Inhibitors / pharmacology*
  • Norepinephrine / metabolism
  • Oxidopamine / antagonists & inhibitors
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Serotonin / metabolism
  • p-Chloroamphetamine / antagonists & inhibitors

Substances

  • Biogenic Monoamines
  • Neurotransmitter Uptake Inhibitors
  • Serotonin Uptake Inhibitors
  • Serotonin
  • Nefopam
  • Hydroxyindoleacetic Acid
  • p-Chloroamphetamine
  • Oxidopamine
  • Norepinephrine