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Re: Anyone suffer paradoxical depression with TCAs?

Posted by King Vultan on March 4, 2004, at 12:56:23

In reply to Re: Anyone suffer paradoxical depression with TCAs? » King Vultan, posted by Sad Panda on March 4, 2004, at 11:19:41

> >
>
> Clomipramine is a potent NE reuptake inhibitor too. Clomipramine, Imipramine, Amitriptyline, Dothepin & Doxepin are very similar in their NE reuptake blocking ability.
>
> Cheers,
> Panda.
>
>

In absolute terms, clomipramine's affinity for the NE reuptake transporter is roughly the same as that of amitriptyline and imipramine, but it is about an order of magnitude less than its affinity for blocking serotonin reuptake. OTOH, imipramine and amitriptyline block serotonin and norepinephrine reuptake at roughly the same order of magnitude.

I do not know what Dothepin is, but in vitro, doxepin is slightly weaker in absolute terms in its affinity for the NE reuptake transporter than any of the drugs listed above. In vivo, it is drastically weaker than any of these drugs because doxepin's main pharmacological action is blocking histamine H1 receptors, at which it is one of the most powerful drugs available. Because doxepin's action at blockading NE reuptake lies about three orders of magnitude below its histamine blockade (based on the dissociation constants generated from Richelson's and Seeman's classic studies), doxepin has little or no effect on blocking NE reuptake in the real world, at least at reasonable dosages.

Todd


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poster:King Vultan thread:319923
URL: http://www.dr-bob.org/babble/20040304/msgs/320166.html