Posted by chemist on April 26, 2004, at 0:40:10
In reply to Re: MAOI causes hypotension - What's the mechanism? » King Vultan, posted by chemist on April 26, 2004, at 0:05:46
chemist again....as you know, you can extract K_{i} from K_{M}, for which there are more data...use the lineweaver-burk method....or, alternatively, look at k_{1} in addition to the michalis-menten constant...assuming the usuals for m-m enzyme-substrate specificity...and you will get competitive K_{i}....all the best, chemist
> chemist here...see my comments denoted by ***
>
> > > Todd, can you do me a favor and use your book to retrieve the Ki values at the NE alpha-1 receptor for a few drugs if it is not too much trouble. Hopefully, they will be listed as nanomoles, but if not, I guess I can convert them. I'd like to use them to update my chart.
> > >
> > > imipramine
> ** IC_{50} @ 0.54 micromolar on 5-HT-{3}*****
> **** k_{i} @ 1 nanomolar for potassium-regulated reuptake ******
> ***inhibits human parotid @ 102 nanomolar ****
> > > desipramine
> *** inhibits paroxetine @ 4.4 nanomolar ****
> *** inhibits parotid @ 135 nanomolar ****
> > > amitriptyline
> > > nortriptyline
> > > phenelzine
> **** IC_{50} @ 4.2 micromolar on 5-HT_{3}***
> > > tranylcypromine
> > > fluoxetine
> **** IC_{50} @ 1.3 micromolaron 5-HT_{3} ****
> *** inhibits binding of paroxetine @ 3 nanomolar
> > > sertraline
> **** K_{D} 0.57 nanomolar to 3.4 nanomolar in comparison to NE uptake**** (!!!) *****
> > > paroxetine
> ***inhibits CYP2D6 @ 0.15 micromolar conc.***
> *** inhibits @ 0.73 nanomolar in comp. to NE ***
> > > venlafaxine
> **** K_{i} for NE @ 1.26 micormolar, @ 74 nanomolar for 5-HT ****
> > > bupropion
> > > mirtazapine
> > >
> > >
> > > Thanks. I know it's a lot, but I tried to keep it to a minimum. Of course, if you would like to add more, I wouldn't complain! :-) I would love to find this book at the book store to see if it is worth buying. What do you think? Unfortunately, money is an issue. The first book I would consider investing in would be one of Stephen Stahl's Essential Pharmacology books. I'm not sure which one to get though.
> > >
> > > There's "Essential Psychopharmacology : Neuroscientific Basis and Practical Applications" and "Essential Psychopharmacology of Depression and Bipolar Disorder"
> > >
> > > This is the first time I'm using the double quote feature. I hope it works.
> > >
> > >
> > > - Scott
> >
> > Unfortunately, "Psychotropic Drugs" does not have the actual Ki values but rather has one of those charts with +'s, with the +'s based off the actual Ki values from those two classic studies. I like the chart because it lists a fairly wide variety of drugs and the receptor affinities cover seven orders of magnitude, but it is not as good as having the actual numbers. Some people, such as my pdoc, would also take at least some exception to it because it is based off of rodent data, and apparently there are some newer studies involving cloned human cells that may be better. I do have access to a study with actual Ki values for some of the drugs you mentioned that are in either rodent or human cadaver tissue, depending on the receptor. I can try to post the info tomorrow you asked for.
> >
> > Of the books you mentioned, "Essential Psychopharmacology" is truly excellent, and I have learned just a ton of things from reading it. The easy to read diagrams make it a good choice for the interested layman, while there is also enough detail to be valuable to even professionals, I believe. It seems clear from some of the anecdotes I've read here that there are doctors out there who could do with a careful reading of this book.
> >
> > Todd
>
>
>
> best, chemist
poster:chemist
thread:339531
URL: http://www.dr-bob.org/babble/20040423/msgs/340038.html