Posted by SLS on October 22, 2016, at 7:39:33
In reply to Re: managing desipramine insomnia - again., posted by cakethread on October 22, 2016, at 0:27:03
> > > Actually instead of clonidine (alpha-1) my doc gave me prazosin (alpha-2) to take with the desipramine at night.
> >
> > Prazosin is a NE alpha-1a/b/d receptor blocker that can be taken all day long (t.i.d.) at 30-40 mg/day without blocking the therapeutic effects of desipramine or producing sedation. It is extremely clean except for its tendency to reduce sex-drive. Prazosin can produce dizziness early in treatment, but it usually disappears.
> >
> > I am going to assume that you already tried nortriptyline.
> >
> >
> > - Scott
>
> Hey,
>
> I'm curious how this works. Isn't the primary mechanism of action of desipramine as a norepinephrine re-uptake inhibitor? In that case, wouldn't blocking alpha receptor subtypes have a cancellative effect?That's a great question. I could only guess what's going on pharmacologically. So, instead of guessing at this point, I can offer you empirical observations of what I have experienced. While taking prazosin, I have taken nortriptyline and desipramine. Desipramine feels the same to me with or without prazosin. It's antidepressant effect was not affected negatively. The same is true for nortriptyline. If I discontinue either of these two drugs while taking prazosin, I relapse into depression.
As for guessing, it is important to recognize that:
1. Not all NE receptors are alpha receptors.
2. There are postsynaptic NE beta receptors in the brain.
3. It is the beta receptors that becomes downregulated by desipramine.
4. There are NE alpha heteroreceptors that function on neurons that use other transmitters to communicate. For examaple, there are might be NE alpha receptors located on the membrane of serotonin neurons.Some see things as they are and ask why.
I dream of things that never were and ask why not.- George Bernard Shaw
poster:SLS
thread:1090062
URL: http://www.dr-bob.org/babble/20160928/msgs/1092715.html