Document Detail


Comparison of nitric oxide synthase inhibitors, phospholipase A2 inhibitor and free radical scavengers as attenuators of opioid withdrawal syndrome.
MedLine Citation:
PMID:  17989510     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chronic morphine-induced withdrawal syndrome after morphine cessation remains a severe obstacle in the clinical treatment of morphine. Previous studies have shown that nitric oxide synthetase (NOS) inhibitors may have therapeutic potential in morphine withdrawal in humans. The mechanisms that underlie expression of morphine-induced withdrawal syndrome are, however, not yet fully understood. Therefore, this study was designed to determine the mechanism of the expression of morphine-induced withdrawal syndrome in mice. Morphine-dependent mice showed marked body weight loss and several withdrawal signs after naloxone challenge. Pretreatment with a NOS inhibitor, such as N-nitro-L-arginine methyl ester (L-NAME) or 7-nitroindazole, but not aminoguanidine, significantly attenuated the expression of morphine-induced withdrawal syndrome. Furthermore, mepacrine (a phospholipase A2 inhibitor) significantly attenuated the morphine-induced withdrawal syndrome in a manner that was different than that with a NOS inhibitor. These results suggest that nNOS and phospholipase A2, which might increase free radicals, play an important role in the expression of morphine-induced withdrawal syndrome. On the contrary, free radical scavengers (including fullerenes, ascorbate-2-phosphate, and DL-alpha-tocopheryl phosphate) attenuated the expression of the morphine-induced withdrawal syndrome. These results indicate that free radicals play an important role in the expression of physical dependence on morphine, and fullerenes could be a potential clinical tool in the relief of morphine withdrawal syndrome.
Authors:
Tomohisa Mori; Shinobu Ito; Kenji Matsubayashi; Toshiko Sawaguchi
Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Behavioural pharmacology     Volume:  18     ISSN:  0955-8810     ISO Abbreviation:  Behav Pharmacol     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-11-08     Completed Date:  2008-01-24     Revised Date:  2009-07-07    
Medline Journal Info:
Nlm Unique ID:  9013016     Medline TA:  Behav Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  725-9     Citation Subset:  IM    
Affiliation:
Department of Legal Medicine, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Ascorbic Acid / analogs & derivatives,  therapeutic use
Enzyme Inhibitors / therapeutic use*
Free Radical Scavengers / therapeutic use*
Hydroxyl Radical
Male
Mice
NG-Nitroarginine Methyl Ester / therapeutic use
Naloxone / pharmacology
Nitric Oxide Synthase / antagonists & inhibitors*
Opioid-Related Disorders / drug therapy*
Phospholipases A2 / antagonists & inhibitors*
Substance Withdrawal Syndrome / drug therapy*
Superoxides / metabolism
alpha-Tocopherol / analogs & derivatives,  therapeutic use
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Free Radical Scavengers; 11062-77-4/Superoxides; 23313-12-4/ascorbate-2-phosphate; 3352-57-6/Hydroxyl Radical; 38976-17-9/alpha-tocopherol phosphate; 465-65-6/Naloxone; 50-81-7/Ascorbic Acid; 50903-99-6/NG-Nitroarginine Methyl Ester; 59-02-9/alpha-Tocopherol; EC 1.14.13.39/Nitric Oxide Synthase; EC 3.1.1.4/Phospholipases A2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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