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Re: Hey Chemist - British MDs and Benzos? awatts

Posted by chemist on April 26, 2004, at 21:11:30

In reply to Re: Hey Chemist - British MDs and Benzos?, posted by awatts on April 26, 2004, at 19:56:57

> > > I thought Xanax was a benzo. What is Xanax if not a benzo? How does it differ from benzos.
> > >
> > > awatts
> > >
> > hi awatts, xanax (alprazolam) is a triazolobenzodiazepene; the benzos lorazepam, diazepam, clonazepam are so-called 1,4-benzodiazepines (this refers to the positions of 2 notrogens found in a 7-membered ring); a benzo you might have in the uk is clobazam (brand names frisium and urbanol, if i recall), and this is a 1,5-benzodiazepene. now, you can hang various things off of the (usually) 3 rings in a typical 1,4 or 1,5 benzo, such as methyl groups, nitro groups, and halogens being popular. alprazolam is a 1,4-benzo that has an extra *ring* attached to it, as opposed to other *groups* or even atoms (H, Cl, F). this ring makes alprazolam special in that although it ``looks like'' the benzos, it is not quite, and your receptors know this very, very well. the pathway by which it is metabolised (thought i'd go with the british version, leave out the zed) is similar to the benzos, but again, not quite. the presence of that ring adds what we call hydrophobic character, which means it becomes less soluble in water and more soluble in fat. this is good news for quick onset of action, as the metabolites of alprazolam have added groups that make the metabolites more water-soluble - so they can cross the blood/brain (water/fat) barrier, and the parent compound - which is much less water-soluble - takes longer to cross the barrier but once it does, it binds very tightly (as do at lest one of the metabolites) to (at least) the GABA A-type receptor, and thus the anxiolytic effects. there are anti-depressant effects that are attributable to alprazolam, and i am uncertain as to what receptors are involved, and equally uncertain about binding affinity for serotonin, dopamine, and norepinephrine receptors, although i would think some affinity for 5-HT_{1A} and D_{2}.....all the best, hope this helps, and do let me know......chemist
>
> Thanks, chemist, you cleared up several things for me. It's interesting that there is so much uncertainty in a mature discipline like organic chemistry. It's not exactly quantum physics so should not be so difficult - no? With chemistry, don't you guys pretty much know all the laws and rules?
>
> awatts
>
>
well, my ph.d. work was in applied math and quantum physics, i took on pharmaceutical chemistry after (another degree, yes). things are more cut-and-dried in quantum physics, with drug interactions and biochemistry it is much more complicated. there are enzymes, genetic differences in individuals, races, genders...and of course, it is a reality that most prescribing docs skipped their classes on pharmaceutical chemistry and listen to what the drug reps tell them. and the issues in making a drug that is viable are huge: you might think that by altering a known quantity by a single atom will increase binding affinity, but in reality, it turns out to be teratogenic or worse. go figure. all the best, chemist

p.s. if you want to talk quantum physics, we can talk!!!!


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