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Re: wash-out before maoi

Posted by King Vultan on May 24, 2004, at 8:03:25

In reply to Re: wash-out before maoi King Vultan, posted by Sad Panda on May 23, 2004, at 1:33:07

> >
>
> Trazodone, Serzone & Nortriptyline are all 5-HT2A & Alpha-1 NE blockers, I'd be interested to know which receptor blockade causes you grief. A Remeron trial could be revealing, it stands out from the other sedating AD's because it doesn't block Alpha-1 NE.
>
> Have you tried the other antihistamine for sleep like Phenergan & Polaramine? Phenergan might be bad, I think it would hit a bunch of receptors.
>
> Cheers,
> Panda.
>
>
>

My theory is that it is these drugs' blockade of 5HT-1 receptors that is responsible. For trazodone I have a reference showing these Ki values in order of strength:

alpha-1..... 12 +/- 0.2
5-HT2A..... 20 +/- 1
5-HT1A..... 29 +/- 1
alpha-2..... 106 +/- 2

Furthermore, the trazodone metabolite mCPP shows these Ki values:

5-HT1A..... 16 +/- 0.2
alpha-1..... 97 +/- 3
5-HT2A..... 110 +/- 3

So for the parent molecule, the 5-HT1A blockade is the 3rd most powerful--and of roughly the same order of magnitude as the alpha-1 blockade. For mCPP, the 5-HT1A blockade is by far the most powerful.

So what does this mean? I'm not sure, but I bring it up because the 5-HT1A receptor seems like a strange one for an antidepressant to be blockading. After all, the presynaptic 5-HT1A receptor is the initial target and the postsynaptic 5-HT1A receptor is the ultimate target for SSRIs to stimulate. To me, it doesn't sound like a great idea to be blockading this receptor, but trazodone--and Serzone, which has a very similar pharmacology--obviously work as antidepressants for some people. My theory is that this weird 5-HT1A blockade business is one of the reasons these drugs are viewed by some as marginal antidepressants. I also think that someone like myself who reacts very strongly and quickly to an SSRI will have a greater chance of finding Serzone and trazodone to be disappointing.

As for nortriptyline, I don't have statistical data, but in the receptor chart in "Psychotropic Drugs", its Ki for 5-HT1 blockade, represented by ++, is higher than most of the tricyclics, and it also has only a relatively weak blockade of serotonin reuptake to counterbalance it (its most powerful effect is its blockade of NE reuptake). I found nortriptyline to have kind of a dual action, as in one way I was getting a lift, and in another I was going down in the dumps. There was enough lift, however, that there was a net antidepressant effect.

None of this appears to apply to Remeron, which my book shows has zero effect on blockading 5-HT1A receptors. I'm more optimistic that this drug would have antidepressant effects for me, but I am not enthusiastic about trying it due to possible oversedation and weight gain problems.

Todd


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URL: http://www.dr-bob.org/babble/20040521/msgs/350074.html