Psycho-Babble Medication Thread 929841

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augmenting buspirone with melatonin

Posted by iforgotmypassword on December 18, 2009, at 15:19:28

does anyone have much understanding of how melatonin potentiates 5-ht1a receptor responses? (if i am even under the right initial impression that this is the case.) what kind of doses may be helpful to augment buspirone if it can do this? is it via the melatonin 1 or 2 receptors, or via some other mechanism?

the concept is interesting me for a few reasons:

all my life i have slept with a bright light on. i cannot sleep in the dark.

i have been reading about correlations between pineal "calcifications" (i have a lesion, presumed to be a cyst), presumed dysfunction in melatonin synthesis, and tardive dyskinesia. i wonder if may apply to tardive syndromes in general.

certainly my accidental buspirone megadosing experience let me feel the most natural, aware, unafraid and sober i have ever in a very long time. maybe i need such high doses as the 5-ht1a receptors lack a piece of the puzzle in allowing them to function normally?

 

Re: augmenting buspirone with melatonin » iforgotmypassword

Posted by SLS on December 18, 2009, at 17:49:16

In reply to augmenting buspirone with melatonin, posted by iforgotmypassword on December 18, 2009, at 15:19:28

> certainly my accidental buspirone megadosing experience let me feel the most natural, aware, unafraid and sober i have ever in a very long time.

Have you tried Remeron?

The reason I ask is because the metabolite of buspirone, 1-PP, is a NE alpha-2 antagonist similar to Remeron. Perhaps this metabolite accumulated in large enough amounts when you took too much buspirone and produced an effect similar to Remeron.


- Scott

 

Re: augmenting buspirone with melatonin » SLS

Posted by iforgotmypassword on December 19, 2009, at 21:40:33

In reply to Re: augmenting buspirone with melatonin » iforgotmypassword, posted by SLS on December 18, 2009, at 17:49:16

I can't believe i forgot to submit this:

I have tried mirtazapine, including with buspirone, just recently; no real effect apart from sleeping longer and an increase in hunger. Pindolol augmentation similarly led nowhere. I didn't use either for long, but I can't keep up with long drug trials. I need something to aid me with my functioning, I don't have any clear space in my apartment, and when I am not exhausted it is often very hard to initiate any activity, and then if I do, to remember what I am doing.

During the short period when I responded to buspirone, I would have had less 1-PP in my bloodstream at the time I gather, as the "megadose" I took was from taking buspirone right after discontinuing nefazodone (a strong 3A4 inhibitor.)

I cannot stress how much it was the most normal I have ever felt in a very long time, perhaps ever. It makes me wonder if gepirone was in part due to it becoming known as a drug that might help with "atypical depression", a diagnosis not taken seriously in any reliable sense, and in Japan tandospirone is used for "neurosis". They potentially help patients who are often poorly regarded by North American thinking, especially by professionals, therefore to them gepirone could either have "helped people who refuse to help themselves", or it must simply be abusable.

I wonder if there are any other 5-ht1a agonists currently in any company's pipelines other than piclozotan. It seems 5-ht1a agonism continues to be looked at as having potentially useful antidyskinetic and antiparkinonian effects, and also as a neuroprotective to improve outcomes after stroke or injury. Unfortunately piclozotan is only in Phase II.

It seems the lack of selectivity may be the root of the efficacy problems with these drugs. Partial dopamine receptor agonism seems to go straight for the autoreceptors, depleting dopamine. This may subtract from the desired therapeutic effect, when an important mechanism of therapeutic 5-ht1a agonism may be how it is indirectly dopaminergic. Another drug of a similar type and intended indication (sarizotan?) also had dopamine receptor affinity and apparently had efficacy issues.

 

Re: augmenting buspirone with melatonin

Posted by SLS on December 20, 2009, at 6:02:36

In reply to Re: augmenting buspirone with melatonin » SLS, posted by iforgotmypassword on December 19, 2009, at 21:40:33

Regarding Abilify (aripiprazole):

> Partial dopamine receptor agonism seems to go straight for the autoreceptors,

I was under the impression that the DA receptor partial agonism was specific to postsynaptic receptors, and that Abilify acted as a full antagonist at presynaptic autoreceptors. Where can I find out more about this?


- Scott

 

Re: augmenting buspirone with melatonin » SLS

Posted by iforgotmypassword on December 21, 2009, at 15:20:29

In reply to Re: augmenting buspirone with melatonin, posted by SLS on December 20, 2009, at 6:02:36

try to find anything that details its effects on dopaminergic firing from the VTA, and explains why...

this is what makes buspirone so awkward two mechanisms that do the opposite.

 

Re: augmenting buspirone with melatonin

Posted by Brainbeard on December 26, 2009, at 14:24:03

In reply to augmenting buspirone with melatonin, posted by iforgotmypassword on December 18, 2009, at 15:19:28

For what it's worth, I've seen more anecdotes on the internet of people having rave experiences on their first day(s) on buspirone. These experiences do not seem to be repeatable. What causes them in the first place may never be elucidated.


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