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Re: Benzodiazepines - Destruction of brain- chemis » sdb

Posted by chemist on May 22, 2005, at 11:40:03

In reply to Benzodiazepines - Destruction of brain- chemist, posted by sdb on May 21, 2005, at 11:35:03

> Hi chemist,
>
> Thanks for your information I will check it, when spare time is available. In medical school benzodiazepines education touch only the surface. You learn a lot of pharmakinetics, indications, and blabla but it is a poor fact that good quality knowledge about these receptors is rare (we are at the beginning to understand mechanisms of receptors, their substructures and role to the ligands. I will follow the interesting research as much as possible. We have extensive research in GABA-Receptors here at the institute). All I know in "practice" is that anterograde amnesia is mostly reversible (this is what most md's say in practice). But as always there are individuals right or left of the gauss curve and loss of memory could have other reasons e.g. age, problems with acetylcholine
>
> Regards
>
> sdb
>


hello there, chemist here...interesting you should mention ACh, it is (as you know) one of the ``hot'' targets...and the GABA studies at your institute - none of my business, of course, although i hope you are rubbing elbows with changeux or sussman or sixma or dougherty, if the institute is in pasadena - place you quite well...for the sake of returning with some pubs that have (as i am sure you and others know) broken new ground in sequence homology structure/function quantification for LGICs with quite impressive overlap in a.a.. sequence...

brejc et al. 2001. Nature 411, 269-276 (in my opinion, a very nice paper indeed, and very thorough alignment data - clear and well-thought - for AChBP with 5-HT$_{3}$, GABA$_{\rm A\,C}$, and glycine receptors, not to mention human ~ mollusc connection!);

miyazawa et al. 2003. Nature 423, 949-955 (another ``wow'');

something by henchman...out of mccammon's group (UCSD), perhaps 2003, late (?)...a docking study with alpha$_{7}$ and (i think) ACh...but there are numerous other mccammon pubs along this line, brooks (b., not c.) too...

grutter, le nov\`ere, and changeux (pick any of them);

one i like for the jumble of science words, nice work, and a twist on alzheimer's and nornicotine by dickerson and janda, 2003. PNAS Early Edition, pnas.1332847100...where else will you find APP, an actual reference to Alzheimer's 99-year-old pub, a tie-in between alzheimer's and the maillard reaction, a cameo from a schiff base, and an amadori rearrangement? how they missed the goldberg variations, i shall never know...yet very nice, if you have not read it, with high detail of mechanistic putative channel for glycation of A$\beta$, specifically where the $\beta$-sheet secondary structure is evident - KLVFF - and there you have it, slow-going on the fibrils courtesy of K, and an open door for diabetes mellitus and such...

all the best, chemist


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