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Re: How are reuptake ratios expressed?

Posted by sowhysosad on April 5, 2009, at 22:24:12

In reply to How are reuptake ratios expressed?, posted by sowhysosad on April 5, 2009, at 22:14:47

> > Effexor has changing ratios as the dose changes...increased affinity for NE at higher doses. But no matter how you look at it, 1:30 or 1:200, yeah, it is basically a glorifed SSRI with not much effect on NE. I believe when they measure brain increases of NE and DA, Prozac actually does more of that than Effexor.
> >
> > Exteme agitation. Yeah, that stinks. I don't know what causes that. Some would say that is a sign of bipolar. I think it could be any number of things. In any case, it basically tells me that whatever that med is, it is probably an offensive one for that person's particular biochemistry. Sometimes slow lengthened titration allows adaptation to be smoother so the agitation isn't severe and eventually is nonexistent. I've never had the strength to endure a med that felt that bad. My instincts just say..."poison!"
> >
> Am I misunderstanding how reuptake ratios are interpreted? I'd always assumed that 1:200 5HT:NE would mean that blockade of the NE transporter was 200x greater, yielding a more noradrenergic effect.
> With regard to the agitation from Effexor, I'd assumed it was because of the norepinephrine boost.
> However, if I'm misinterpreting the ratios, it's gotta be the same phenomenon as SSRI startup anxiety. As I understand it, it's over stimulation of one of the 5HT2 receptor groups (A or C I believe), which normally subsides when the receptors downregulate.

I think I've sussed it: the ratios relate to inhibitor affinities expressed in Ki nM.

In Ki nM a LOWER number is BETTER, so the normal logic of a ratio is reversed, ie. the lower value in the ratio represents the higher affinity.

Am I right boffins?

If so, that would explain why I've found imipramine to be so unpleasantly noradrenergic. I'd assumed its 2:1 5HT:NA ratio to mean it favoured serotonin, which is why I asked the doc for it instead of clomipramine which is 1:2!




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