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Re: managing desipramine insomnia - again. - Oops

Posted by SLS on October 22, 2016, at 8:17:34

In reply to Re: managing desipramine insomnia - again., posted by SLS on October 22, 2016, at 7:39:33

*** Sorry. I submitted my post accidentally before I had a chance to finish it.

__________________________________________


> > > > 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.

> > 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 30 mg/day, I have taken nortriptyline and desipramine. Desipramine feels the same to me with or without prazosin. Its 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.

You have given me a lot to think about. 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 become downregulated by desipramine.

4. There are NE alpha heteroreceptors that function on neurons that use other transmitters to communicate. For examaple, there are NE alpha-1 receptors located on the membrane of serotonin neurons.

5. NE alpha heteroreceptors can act as inhibitors of serotonin neurons. Blocking them with prazosin might disinhibit (stimulate) serotonin or dopamine neurons.

6. Prazosin blocks only NE alpha-1 receptors (alpha-1a/b/d), and not beta receptors.

7. It is the NE alpha-2 receptor that acts as an autoreceptor on NE neurons, and not alpha-1 receptors.

I'm not sure prazosin will help with most cases of insomnia. It does, however, inhibit the experience of nightmares associated with PTSD without affecting the time spent dreaming. This effect occurs at very low doses of prazosin - as little as 1-3 mg taken at night.

Please post what you come up with regarding the pharmacology of prazosin. I am missing something. It is my hypothesis that it is the NE alpha-1d receptor that is involved in the anti-PTSD and anti-depressant properties of prazosin.


- Scott


Some see things as they are and ask why.
I dream of things that never were and ask why not.

- George Bernard Shaw

 

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poster:SLS thread:1090062
URL: http://www.dr-bob.org/babble/20160928/msgs/1092716.html