Posted by chemist on August 21, 2004, at 0:53:37
In reply to Re: kp.-benzo least likely to cause cogn. impair.? » alesta, posted by Kon on August 20, 2004, at 22:37:26
hello there, chemist again: i actually do have the paper you referenced. do have a look at the last coloumn in table 1, page 8 in the article you reference. note that, while lipid solubility of diazepam is judged to be greater than that of oxazepam by a factor of two (and yes, i am aware that this compound in particular is the end-game for most 1,4-benzos, but not all) but the binding affinity of the active metabolite - desmethyldiazepam or nordiazepam, your choice - is half that of oxazepam. the alprazolam conundrum - aside from targeting (at least) the omega site in GABA_{A} - is flawed, according to these data: it is indicated to be only slightly more lipophilic than lorazepam - unlikely given the triazolo group present in alprazolam, increasing aromaticity and decreasing solubility in polar solvents - yet binds in the uM range only by a factor of 2.5 times greater than lorazepam. of course, the HPLC data are now 18 years old, as are the numbers for binding affinities: that is a problem with these review articles, especially when every single article in the series (i do have them all) was ``supported by an unrestricted educational grant from Solvay Pharmaceuticals,'' and wouldn't you know that the orally-disintegrating Klonopin wafers marketed by - surprise - Solvay - are mentioned in every article in a positive light. aside from this obvious self-promotion, lorazepam and alprazolam are different chemical entities, yet the data presented herein do not support observed findings in re: memory and cognition, at least from a chemical standpoint. the half-lives of both drugs are quite similar (12-15 hr for A, 10-20 for L, neither with an active metabolite). all the best, chemist
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