Research article summary (published 29 Sep 1993):

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

Full 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.

Author information

Author/s: Fuller, R W (RW); Snoddy, H D (HD);

Affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.

Journal and publication information

Publication Type: Journal Article

Journal: Neuropharmacology (Neuropharmacology), published in ENGLAND. (Language: eng)

Reference: 1993-Oct; vol 32 (issue 10) : pp 995-9

Dates: Created 1994/02/25; Completed 1994/02/25; Revised 2003/11/14;

PMID: 7507578, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

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 Serotonin - metabolism Serotonin Uptake Inhibitors - pharmacology p-Chloroamphetamine - antagonists & inhibitors

Associated Chemicals: Biogenic Monoamines (0) ; Neurotransmitter Uptake Inhibitors (0) ; Serotonin Uptake Inhibitors (0) ; Oxidopamine (1199-18-4) ; Nefopam (13669-70-0) ; Serotonin (50-67-9) ; Norepinephrine (51-41-2) ; Hydroxyindoleacetic Acid (54-16-0) ; p-Chloroamphetamine (64-12-0)

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