The drugs we are talking about are Bretazenil[1] and Pagoclone[2], which are more targeted than GABA agonists - they only bind to certain subtypes of the GABA r

The drugs we are talking about are Bretazenil[1] and Pagoclone[2], which are more targeted than GABA agonists - they only bind to certain subtypes of the GABA receptor. They are also claimed to be partial agonists , meaning even at maximum capacity they only stimulate the receptor to a fraction[3] of a full agonist. One the other hand The potential of abuse of Pagoclone claimed to be similar to that of valium(how did they measure that ?). On the other hand, there's some interesting work on molecules that decrease dependence/tolerance.For example there's work on reducing morphine abuse potential using calcium/magnesium in rats[4].There's also conflicting research results regarding the effect of magnesium, glycine and zinc on the effect alcohol has on the NMDA receptor(which is supposed to be the main cause of tolerance)[5]. So maybe there's a combination that gives most of the benefits of alcohol , with a small dependence potential. Let's not get discouraged from this noble goal yet. [1]http://en.wikipedia.org/wiki/Bretazenil http://en.wikipedia.org/wiki/Bretazenil [2]http://en.wikipedia.org/wiki/Pagoclone http://en.wikipedia.org/wiki/Pagoclone [3]http://upload.wikimedia.org/wikipedia/commons/thumb/d/d2/Agonist_2.png/330px-Agonist_2.png http://upload.wikimedia.org/wikipedia/commons/thumb/d/d2/Ago... [4]http://www.ncbi.nlm.nih.gov/pubmed/19658277 http://www.ncbi.nlm.nih.gov/pubmed/19658277 [5]http://www.ncbi.nlm.nih.gov/books/NBK5284/ http://www.ncbi.nlm.nih.gov/books/NBK5284/