Posted by King Vultan on March 27, 2004, at 12:16:54
In reply to Re: Help: WHICH IS THE LEAST SEDATING SAFETEST TCA? » King Vultan, posted by Sad Panda on March 26, 2004, at 11:02:15
>
> Hi Todd,
>
> My info has Imipramine as less sedating & less anticholinergic than Nortriptyline but giving more orthastatic hypotension. Where are you getting your info from?
>
> Cheers,
> Panda.
>
>
All of my references indicate that imipramine is more anticholinergic in vitro than nortriptyline, but I believe that the dissociation constants are actually roughly equivalent. The problem with imipramine is that its ACh blockade is of the same order of magnitude as its five other main pharmacologic blockades, so that a patient is assaulted with anticholinergic effects even at low dosages. For the same reason, imipramine should generate more orthostatic hypotension at lower dosages than nortriptyline, as this is also of the same order of magnitude as imipramine's ACh blockade.Nortriptyline, OTOH, has a relatively strong NE reuptake blockade that is at least one order of magnitude, and probably more like two orders of magnitude above its ACh blockade. In theory, anyway, a patient would need to take a proportionally larger dose of nortriptyline to experience the same ACh effects as one would on imipramine because the NE reuptake blockade will dominate the pharmacologic profile at low dosages. Grasping this concept is key to understanding how a drug's in vivo behavior (in the body) differs from its in vitro behavior (in the laboratory). There is a ton of information available at www.preskorn.com looking at drug behavior from this perspective.
Well, be that as it may, I've taken nortriptyline and believe I did suffer some anticholinergic effects on it. I'm not really sure, though, because it could just have been sedation from its histamine blockade. Whatever the case, the molecule clearly did not agree with me, in sharp contrast to my experience on the imipramine metabolite desipramine, which is the only drug I've tried that had few enough side effects for me to able to tolerate a full therapeutic dose of it.
Todd
poster:King Vultan
thread:328391
URL: http://www.dr-bob.org/babble/20040325/msgs/329077.html