Posted by ed_uk2010 on February 25, 2012, at 2:43:14
In reply to Re: Adding Parnate and prazosin., posted by sigismund on February 24, 2012, at 17:07:05
> > it was hypothesised than it might augment noradrenergic ADs.
> Because it acted in a similar way or an opposite way or because it mixed well (and so on and so forth)?
Prazosin does block the effects at NE, but only at one type of receptor (alpha-1 group). It doesn't block the effects of NE at any other type of receptor. Perhaps it could 'augment' noradrenergic ADs such as nortriptyline by allowing the increased levels of NE to bind to other receptors but not alpha-1?
TCAs also block alpha-1 receptors but like Scott said, they are not very potent at the alpha-1b subtype, which may be the relevant receptor in the brain. TCAs are more active at alpha-1a, which is why they tend to reduce standing BP.
Interestingly, reboxetine, an NRI which does not block alpha-1 receptors at all, does not appear to be such a reliable AD as nortriptyline. Reboxetine is highly selective for the NE transporter whereas nortriptyline also binds to a variety of other receptors. Lack of alpha-1 blockade also means that reboxetine can make it difficult to urinate. This is less of a problem with nortriptyline because it blocks alpha-1a receptors in the prostate and urinary tract.