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Searching for perfect sleep: the continuing evolution of GABAA receptor modulators as hypnotics
David J Nutt
Department of Neuropsychopharmacology and Molecular Imaging, Imperial College London, London, UK, firstname.lastname@example.org
S M Stahl
University of California San Diego, School of Medicine, San Diego, CA, USA
The non-benzodiazepine GABAA receptor modulators (‘Z-drugs’) — zaleplon, zolpidem, zopiclone and eszopiclone — have become the accepted treatments for insomnia where they are available. However, recent randomized, placebo-controlled trials suggest that, for these drugs, there may be particular efficacy and tolerability profiles and distinct clinical outcomes in specific patient populations. This is particularly apparent when hypnotic/ selective serotonin reuptake inhibitor co-therapy is used to treat patients with co-morbid insomnia and psychiatric disorders, as patient recovery appears to be accelerated and enhanced by some drugs but not others. Emerging evidence of why this should be the case is that these hypnotic drugs may differ significantly from each other in their pharmacodynamic and pharmacokinetic profiles. Functional selectivity for specific GABAA receptor subtypes may determine each drug’s clinical attributes, while the pharmacokinetic characteristics of Z-drugs also determine to a large extent how they perform in the clinic. For example, activity at GABAA alpha 1 receptor subtypes may be associated with sedative effects, whereas activity at alpha 2 and alpha 3 receptor subtypes may be associated with anxiolytic and antidepressant effects. In summary, the distinct clinical outcomes of zaleplon, zolpidem, zopiclone and eszopiclone may be explained by each drug’s unique GABAA receptor subunit selectivity and pharmacokinetic profile. Further investigation of GABA A receptor subtype effects would help to increase understanding of current hypnotic drug effects, while knowledge of each drug’s specific binding profile should enable clinicians to tailor treatment to individual patient’s needs.
Originally posted by Dr Expired
I can empathise with anyone who cannot sleep when tired.
In Australia Doxylam is a legal over the counter remedy available at most chemists, you should fall asleep after taking the prescribed dose of this relatively non addictive drug .
Please note alchohol will keep you awake and work against the sedative effects of Doxylaml once the alcohol wears off.
It is very unwise to drink booze with any sleeping aid.
The only strange side affect I have encountered with Doxylam is aural hallucinations whilst asleep or near asleep.edit on 25-6-2011 by Dr Expired because: (no reason given)
Originally posted by Dr Expired
reply to post by Imhere
Yes alcohol can send us to sleep, but it is not a restful sleep as our livers and kidneys heart are working to de toxify us.
The point I was making was alcohol can negate the potency of certain sleeping drugs.
And that the two should not be mixed.