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Lack of Tolerance Observed to Hypnosedative Actions upon Repeated Treatment with the Novel Hypnosedative Zopiclone (Cyclopyrrolone) in Animal Models for Hypnosedation
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Background
Benzodiazepine (BZD) hypnosedatives are widely used for treatment of insomnia and anxiety, since last 5-6 decades. Large number of BZD analogues has been synthesized to obtain superior risk/benefit ratio since then. Most of the BZDs have similar pharmacological actions; however they lack in specificity and associated with the problem of tolerance, rebound insomnia and anxiety disorders which have necessitated the search for alternatives. Zopiclone is a newer Hypnosedative chemically unrelated to benzodiazepines; binds with high affinity to benzodiazepine receptors at the site close to rather than identical to the site occupied by BZDs. Results of the earlier studies are most contradictory since, some studies reported that Zopiclone has less potential to develop tolerance, rebound insomnia and anxiety disorders on regular use than benzodiazepines and some reported even greater potential to develop these side effects than benzodiazepines. Present study was therefore designed to investigate whether tolerance is developed to hypnosedative activity on repeated administration of Zopiclone (7.5 mg/kg) daily.
Experimental approach
For evaluation of development of tolerance to its hypnosedative actions animals were treated with respective drug i.e. control group (0.1ml NS), standard group (Lorazepam 5mg/kg p.o.) and test group (Zopiclone 7.5mg/kg p.o.) for 10 consecutive days; and on 10th day Pentobarbitone sleeping time potentiation & Elevated plus maze performance test were performed. The observations of 10th day compared with observations on day one.
Results
Zopiclone (7.5 mg/kg) on chronic administration did not develop tolerance to hypnotic activity; instead this activity was increased but it was statistically insignificant i.e. P>0.05. Similar results were observed for anxiolytic activity.
Conclusions
Zopiclone can be recommended as substitute for conventional hypnosedative for short term (1 - 4 weeks) treatment of insomnia, or alternatively, long term infrequent treatment of insomnia.
Keywords
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