2004 - Memantine Alcohol Trial
Reference 1.
Author(s): Warnecke M, Koller G, Mayer C, Krystal JH, Schuetz CG
Title: Combining naltrexone and memantine to block the rewarding effects of alcohol: an experimental pilot study in human subjects
Source: Sixty-Sixth Annual Scientific Meeting of College on Problems of Drug Dependence
Date of Publication: 2004
Language: English
Date Created Edited: 18.6.2004
Medline Unique Identifier: <38 Unique Identifier or URL>
Abstract: Rationale:
There is currently a high priority for developing new pharmacotherapy approaches to the treatment of alcoholism.This need was increased by recent data indicating the lack of efficacy of naltrexone treatment in alcohol dependent veterans.Objective:
If naltrexone is to be employed in the treatment of alcoholism, it may be that it will serve as an adjuvant that enhances the efficacy of a drug that is co-prescribed.Supported by results from preclinical work, we have been collecting dat a on the capacity of naltrexone, memantine (an uncompetitive NMDA receptor antagonist), and the combination of naltrexone and memantine to block the rewarding effects of ethanol intoxication in healthy human subjects.
Methods:
Ten healthy outpatient participants recieved pretreatment with 37.5 mg naltrexone or placebo followed by challenges with memantine (0.5 mg qkg IV) or placebo.Additionally, following drug administration the participants consumed three different amounts of alcohol.Drug and alcohol effects were monitored by objective signs - skin conductance, heart rate, temperature, respiration, locomotor activity, Cortisol-, Prolactin- and ACTH levels as well as subjective stimulating and sedative effects.
Results:
Our pilot data in 10 healthy human subjects indicate that memantine and naltrexone, by themselves, influence the basal level of stimulation (naltrexone is mildly sedating while memantine is mildly stimulating,p<0.05).Of greatest interest,
our pilot data suggest that the combination of memantine and naltrexone (but not either drug alone) blocks the dose-related stimulatory effects of ethanol(p<0.05).
Similarly, naltrexone blocks the memantine-potentiation of discriminative stimulus effects of ethanol (i.e., block s the ability of increasing doses of ethanol to be perceived as "more ethanol like",p<0.05).
Conclusion:
Together, these data suggest that naltrexone might be a critical therapeutic adjuvant if memantine or other related drugs are developed as pharma cotherapies for alcohol dependence.
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