Posted by zeugma on February 20, 2006, at 14:48:06
In reply to Re: NRIs are infact dopamine uptakin inhibitors ?, posted by SLS on February 20, 2006, at 13:29:35
Hi Scott.
>
> > COMT pleomorphisms have been associated with ADHD, with response to modafinil, and with cognitive impairment in schizophrenia.
>
> Would these represent an overactivity of the enzyme?The less active COMT enzymes are associated with better response to atypical AP's a nd less severe cognitive impairment in schizophrenia. In ADHD it is paradoxically associated with poorer executive function.
>
> >
> > I think that NE uptake inhibitors have been investigated for the relief of 'negative symptoms' in schizophrenia, by stimulating the D4 receptors on the PFC, while not causing heightened stimulation of the D2 receptors in the accumbens that are responsible for the 'positive' symptoms.
>
> My symptoms overlap greatly with the deficit syndrome seen in schizophrenia. That, and the severity of my cognitive impairments, point to the PFC as a site of dysfunction. I am beginning to more seriously consider rTMS as a modality by which to increase the activity of the left DLPFC.
>I don't know much about rTMS (is that what linkadge was doing?) I have long believed, based no doubt on a crude understanding of brain morphology, that my own symptoms are related to DLPFC dysregulation. In particular, I think it's activated when it's supposed to shut off (during REM) and underactivated when it's supposed to be working (causing a trance-like state during wake). What is the mechanism conjectured responsible for rTMS' stimulation of the DLPFC?
> > In terms of ADHD, atomoxetine is considered more potent than placebo but weaker than methylphenidate or amphetamine.
>
> Statistically speaking, of course, in terms of numbers of "responders" - not in the quality of response.That point is often lost on people who think Strattera is 'weaker' than the other ADHD meds. of course, drug companies take this into account when developing drugs. This means that those who would respond to an unconventional modality- not that Strattera, e.g., is a particularily unconventional drug- are left waiting for the next magic bullet to pass them by :-(
>
> >
>
> Have you ever looked into a drug called mazindol? It is a very potent ligand for the DAT. However, I don't know the extent to which it actually acts as a DA reuptake inhibitor. There has been some debate about this. It might actually act more through NE. It is an approved antiobesity drug still used as a biological probe to assay DAT binding.
>
Mazindol is also used in Europe to treat narcolepsy. It is similar to nomifensine? (which was also looked at for ADHD). Did you find that nomifensine had a positive effect on cognition?> What are your thoughts on sibutramine?
>
Ken Gillman, who operates a site called http://psychotropical.com/, speaks highly of this as an AD, at least when I used to visit his site.Have you ever tried it?
I wonder if D4 ligands have been looked at in depression.
-z
>
> - Scott
poster:zeugma
thread:611154
URL: http://www.dr-bob.org/babble/20060219/msgs/611471.html