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Re: theoretical question: nomifensine vs ritalin/methy

Posted by psychobot5000 on May 29, 2012, at 23:22:16

In reply to Re: theoretical question: nomifensine vs ritalin/methy » psychobot5000, posted by SLS on May 29, 2012, at 20:36:17

> > My whimsy and curiousity leads me to ask this question:
> >
> > Nomifensine and methylphenidate are both norepinephrine and dopamine reuptake inhibitors, without a lot of other known action on other binding sites. However, the one is thought of primarily as an antidepressant (and was apparently quite effective for that purpose), while the other is a psychostimulant with positive effects on mood, but not an antidepressant per se. Why? What difference might there be between the two molecules?
> >
> > To some extent they're similar, i.e. it's usually presumed nomifensine had some positive effect on attention and that sort of thing, as a stimulant would, but on mood they seem to act differently, despite the marked similarity in their pharmacological profiles.
> >
> > Thoughts?
> > pb5000
>
>
> Perhaps there are regional differences in where each drug exerts its effects. I don't know.
>
> Methylphenidate is a bit heavier on dopamine than it is on norepinephrine. I believe nomifensine exerts a more balanced effect. Also, methylphenidate increases the release of dopamine, albeit to a lesser extent via a different mechanism of action than amphetamine. Nomifensine does not. I think the bottom line is to compare the long-term changes these drugs produce in downstream signalling. Methylphenidate increases neural tone and signal-to-noise ratio in certain dopamine circuits almost immediately. With antidepressants, increases in signal-to-noise takes two or more weeks to manifest, at least in glutamatergic circuits.
>
>
> - Scott
>
>
>

Wow. A much better answer than I could reasonably have expected.

Didn't know that methylphenidate was a releasing agent, or that it acted more heavily on DA. Very interesting, all of it. Will have to look up 'neural tone.'


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