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Re: ssri's effect on cognitive functioning???

Posted by chemist on April 9, 2004, at 23:33:21

In reply to Re: ssri's effect on cognitive functioning???, posted by SpaceFairy on April 9, 2004, at 3:05:27

> > Ho do you know if you are unable to metabolize SSRIs ? Is it just SSRIs or any antidepressants ?
> > Thanks
>
> Hi!
>
> Thanks for posting such interesting questions. I had to look in to this a bit further, and I think I have got the answer (but please consult a medical expert, as this is not my area). Basically, if you lack the P450 2D6 liver enzyme this will lead to an inability to metabolise serotongeric and tricyclic antidepressants. MAOI's are implicated with the enzyme, but the only info that I can find is surrounding the long established risk of mixing them with other drugs. New methods have been developed to detect the ability through something called cytochrome P450 2D6 (CYP2D6) genotyping. That's the science bit (just in case you wanted to look the key words up through a search engine). One link is
> http://www.preskorn.com/books/ssri_s7.html?print=1
>
> Now - what it means for us! As far as I am aware, this can be done through analysis of our blood. If I'm right this could have massive implications - a simple blood test before prescribing antidepressants could predict the probability of experiencing a negative reaction. As I say, this is not really my field so I'm not 100% sure - & also, it seems so simplistic that I would imagine that it would have been in place already what with all the controversy & everything.
>
> I'll post a couple of message around the experts & see what response I get back & let you know.
>
> Take care,
>
> Space Fairy
>
chemist here...there is a bit of misinformation above: monoamine oxidase inhibitors are antagonists for the enzyme monoamine oxidase. the mechinism my which this enzyme works is by deaminating drugs with a secondary or tertiary amine, as found in phenethylamine derivatives such as parnate and nardil. monoamine oxidase is prevalent throughout our bodies, and if you are taking an MAOI, you risk hypertension/stroke due to excessive buildup of the ``unmetabolized'' parent compund, which is most pronounced for CNS agents such as Nardil and Parnate. as for metabolism of SSRIs and others: it is most common that the parent compund is not the psychoactive agent - e.g., diazepam (valium) is metabolized to nordiazepam which does the work - and SSRIs are not autoinducers of CYP450A (i generalize) and you need not worry about cognitive impairment, as this is *strongly* tied to agonism of neuronal nicotine receptors, which are implicated in alzheimer's, parkinson's, and schizophrenia. now, i have to say that most SSRIs are metabolized via the CYP 450 2D6 enzyme, although this is of import if you are taking tricyclics, which you are not. if you have liver disfunction, it is prudent to play it safe, but in general, the SSRIs of yesteryear and today are very safe....best, chemist


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