Posted by SLS on February 20, 2006, at 13:29:35
In reply to Re: NRIs are infact dopamine uptakin inhibitors ? » SLS, posted by zeugma on February 20, 2006, at 13:02:52
Hi Z.
You said a mouthful!
> 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?
> Overexpression of DA transporters, along with underexpression of D4 receptors, would conceivably cause additive effects and result in some of the more severe phenotypes of ADHD.
> One theory, based on an animal model, holds that ADHD is a hypernoradrenergic, hypodopaminergic state.
That sort of makes sense to me. It's an interesting idea.
> 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.
> 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.
> But it can be effective in those who have poorer responses to methylphenidate, at least, because overexpression of the DA transporter has been associated with MPH nonresponse (makes sense). In any case I have found atomoxetine to be the most 'stimulant-like' of the drugs I have taken.
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.
What are your thoughts on sibutramine?
- Scott
poster:SLS
thread:611154
URL: http://www.dr-bob.org/babble/20060219/msgs/611435.html