PubMed · 741403
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
H Barrière. 1978. [Mutilating acropathies].. https://pubmed.ncbi.nlm.nih.gov/741403/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Explore the source record for details and available documents.
Pharmacotherapy treatment for alcoholism is limited by poor compliance, adverse effects, and fluctuating drug levels after bolus administration. A long-term delivery system would improve upon these limitations. The current study describes the characterization of a sustained release implant containing nalmefene, an opioid antagonist, for treatment of alcoholism. Nalmefene was blended with ethylene vinyl acetate (EVA), extruded into 2.8 mm x 27 mm rods, and coated with EVA to optimize release. In vitro release was determined by HPLC, and in vivo release characteristics after subcutaneous implantation into rats were determined by LC-MS/MS analyses. Extrusion produced rods containing 80.09 +/- 6.0 mg nalmefene. In vitro release was high from the uncoated rods, and they were depleted of drug fairly quickly; however EVA coatings maintained release over longer periods. The 25 wt.% coated rods provided in vitro release of 0.36 mg/day/rod, and in vivo release of 0.29 mg/day/rod over 6 months, and showed dose-dependent nalmefene plasma concentrations (one rod: 3.33 +/- 0.56 ng/ml, three rods: 10.19 +/- 2.31 ng/ml). After explantation, nalmefene plasma concentrations were undetectable by 6 h. A sustained release nalmefene rod provides 6 months of drug with no adverse effects.
1. Chronic alcohol exposure modifies endocannabinoid levels in different brain regions, while pharmacological targeting of the endocannabinoid system has been reported to influence ethanol intake in laboratory animals. 2. The present study was aimed at evaluating the pattern of changes of endocannabinoids and their receptors, with emphasis on reward-related brain areas, in Wistar rats subjected to consecutive phases of alcoholization, alcohol deprivation (abstinence), and voluntary consumption of alcohol (relapse). 3. We observed that, in the limbic forebrain, anandamide (AEA) and 2-arachidonoylglycerol (2-AG) contents increased after 7 days of alcoholization, then to dramatically decrease after 48 h of alcohol deprivation and, in the case of 2-AG, to further decrease when rats were allowed to relapse to alcohol consumption. By contrast, in the midbrain, there was a marked reduction in AEA, but not 2-AG, content, after alcoholization. This decrease was not affected during alcohol abstinence, but both AEA and 2-AG contents were then significantly reduced when rats were allowed to relapse to alcohol consumption. 4. Based on these data, we examined whether pharmacological activation/blockade of endocannabinoid transmission might influence ethanol intake in rats allowed to relapse to alcohol consumption after subsequent periods of alcoholization and alcohol deprivation. 5. Treatment with either Delta(9)-tetrahydrocannabinol or CP55,940, two cannabinoid agonists, reduced both total liquid and ethanol intake but did not affect ethanol preference. Treatment with SR141716, a selective cannabinoid CB(1) receptor antagonist, also produced a significant reduction in both total liquid and ethanol intake without affecting ethanol preference. Accordingly, none of these effects on ethanol intake were accompanied by changes in dopamine and GABA in limbic structures. 6. In summary, the levels of endocannabinoids underwent significant changes in reward-related areas during alcoholization, alcohol deprivation, and relapse, showing the lowest values in this latter phase. Treatment with cannabinoid agonists or a selective CB(1) receptor antagonist resulted in a reduction of ethanol intake by rats allowed to relapse to alcohol consumption after periods of alcoholization and alcohol deprivation, but these effects did not appear to be due to changes in neurobiological substrates currently involved in alcohol reinforcement/relapse.