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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 8 of 8. This is the beginning of the thread.
Posted by aazospiro on March 25, 2004, at 18:17:45
Benadryl knocks me out cold so does chlorpheniramine. Amitriptyline 10 mg makes me buzz, space out and heavy all over. Which is the best TCA for AADHD. Would imipramine, nortriptyline, desipramine or protiptyline be better or offer more advantages or stimulants?
Posted by King Vultan on March 25, 2004, at 20:29:58
In reply to Help: WHICH IS THE LEAST SEDATING SAFETEST TCA?, posted by aazospiro on March 25, 2004, at 18:17:45
> Benadryl knocks me out cold so does chlorpheniramine. Amitriptyline 10 mg makes me buzz, space out and heavy all over. Which is the best TCA for AADHD. Would imipramine, nortriptyline, desipramine or protiptyline be better or offer more advantages or stimulants?
Desipramine probably has the fewest side effects of any of the tricyclics, is the least anticholinergic, and does have some utility for adult ADD. Protriptyline is the most stimulating of the TCAs but is rather anticholinergic, unfortunately. Nortriptyline and imipramine are more sedating than either of these drugs; nortriptyline is the 2nd least anticholinergic tricyclic, while imipramine has significant anticholinergic properties, being notorious for dry mouth, for instance.Todd
Posted by Sad Panda on March 26, 2004, at 11:02:15
In reply to Re: Help: WHICH IS THE LEAST SEDATING SAFETEST TCA? » aazospiro, posted by King Vultan on March 25, 2004, at 20:29:58
> > Benadryl knocks me out cold so does chlorpheniramine. Amitriptyline 10 mg makes me buzz, space out and heavy all over. Which is the best TCA for AADHD. Would imipramine, nortriptyline, desipramine or protiptyline be better or offer more advantages or stimulants?
>
>
> Desipramine probably has the fewest side effects of any of the tricyclics, is the least anticholinergic, and does have some utility for adult ADD. Protriptyline is the most stimulating of the TCAs but is rather anticholinergic, unfortunately. Nortriptyline and imipramine are more sedating than either of these drugs; nortriptyline is the 2nd least anticholinergic tricyclic, while imipramine has significant anticholinergic properties, being notorious for dry mouth, for instance.
>
> Todd
>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.
Posted by Keith Talent on March 27, 2004, at 2:02:25
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
Clomipramine and nortriptyline don't sedate me at all. Desipramine might be what you're after, but I haven't tried it - it's not available in Australia.
Posted by Sad Panda on March 27, 2004, at 11:54:24
In reply to Re: Help: WHICH IS THE LEAST SEDATING SAFETEST TCA?, posted by Keith Talent on March 27, 2004, at 2:02:25
> Clomipramine and nortriptyline don't sedate me at all. Desipramine might be what you're after, but I haven't tried it - it's not available in Australia.
>
>Hi Keith,
I live there too. Do you know what the reason is we can't have Desipramine here? I think it would be a good add on to an SSRI, certainly as good as Wellbutrin, which we can't have either. :/ Might be usefull to the ADHD types too.
Cheers,
Panda.
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
Posted by Sad Panda on March 27, 2004, at 13:00:17
In reply to Re: Help: WHICH IS THE LEAST SEDATING SAFETEST TCA? » Sad Panda, posted by King Vultan on March 27, 2004, at 12:16:54
>
> >
> > 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
>I overlooked another factor too. Dosages of the secondary TCA's are lower than the tertiaries, which would mean less side effects too.
I have read most of www.preskorn.com , It's pretty good.
Cheers,
Panda.
Posted by zeugma on March 27, 2004, at 14:50:48
In reply to Re: Help: WHICH IS THE LEAST SEDATING SAFETEST TCA? » King Vultan, posted by Sad Panda on March 27, 2004, at 13:00:17
>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.>I did not experience any anticholinergic effects from nortriptyline until I got above 50 mg/day. The NE reuptake blockade effects (impulsivity, jitteriness, 'activation') began less than a week after starting the drug at 20 mg/day.
The antihistaminic effects became noticeable at some point between 20 and 50 mg/day. They are relatively weak (for me, anyway) which means that I have to augment with buspirone to get a strong sedative effect.
It is hard to tell what is an anticholinergic effect and what is a 'pseudo-anticholinergic' effect (as Stephen Stahl calls it) from NE reuptake blockade. The symptoms I'm calling anti-cholinergic (constipation, dry skin, dry mouth) became much more frequent and persistent since adding Strattera. Strattera has no direct effect on muscarinic receptors.
>
This is the end of the thread.
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