Did anyone try high doses of buspar?

[crayzyMed]

Apperantly 5HT1A should be a major anxiolytic, so makes me wonder why buspar doesnt work for most of us. Maybe we need to take higher doses?

[jer]

I've tried high doses. it didnt work.

doctors like it because it has least side effects.

It does work for a few people and if it does, then that is the best medication.

[crayzyMed]

Originally Posted by jer

I've tried high doses. it didnt work.

doctors like it because it has least side effects.

It does work for a few people and if it does, then that is the best medication.

Well, is anyone up for 1200mg?
Beleive me or not it was used in that dose in a trial...

[euphoria]

Buspirone (either directly or through its active metabolite) has D2 and α2-blocking effects, in addition to those on the 5-HT1A receptor. These things are probably what make buspirone such a weak anxiolytic and antidepressant, and the receptor profile (or ratio of effects, shall we say) isn't going to change with higher dosage.

Consider that clonidine (an α2 agonist) is used for performance anxiety, opiate withdrawal anxiety, etc. -- the opposite effect is not something you'd seek out for anxiety disorders, but maybe for depression. The D2 receptor is very important for our experience of pleasure, and blocking it (as buspirone / its metabolite does) promotes anhedonia, depression and antipsychotic effects. Even if buspirone's interaction with those receptors is weak, it's not clinically irrelevant.

Really I think buspirone was a flawed drug from the outset, but it obviously works for some people. If I were you, I wouldn't bother megadosing it because the effect on "undesirable receptors" will increase, but maybe (at normal dosage) buspirone could be considered as an augmentation strategy (e.g. with an SSRI). Personally I am waiting for better meds to target 5-HT1A; they are in development.

[TiMeZuP]

Originally Posted by euphoria

Personally I am waiting for better meds to target 5-HT1A; they are in development.

How would a med targeting 5-HT1A receptor help us with pleasure from dopamine? Isn't the 5-HT1A receptor related to to Serotonin? What meds are in development, can you list your source......

Thanks......

[euphoria]

Originally Posted by TiMeZuP

How would a med targeting 5-HT1A receptor help us with pleasure from dopamine? Isn't the 5-HT1A receptor related to to Serotonin? What meds are in development, can you list your source......

Thanks......

The brain is a very complicated thing, I don't think it could be reduced to that level of simplicity. Imagine (theoretically) something called "neurotransmitter X", it may affect multiple types of receptors in varying locations of the brain, some could increase "neurotransmitter Y" levels, some could decrease them.

The 5-HT1A receptor is a serotonin (5-HT) receptor, and to answer your question, "5-HT1A receptor activation has been shown to increase dopamine release in the medial prefrontal cortex, striatum, and hippocampus" (just from Wikipedia, I know not a source but w/e).

BTW, I was talking about the 5-HT1A agonists listed on here:

http://www.neurotransmitter.net/newdrugs.html

In Japan they already have one in use AFAIK, called tandospirone.

So yeah, I think serotonin receptors are a hugely important target if you have a mood disorder, even if current methods of doing so are still relatively unsophisticated & clumsy.

[crayzyMed]

Does this one look better?

Urapidil is a sympatholytic antihypertensive drug. It functions as an α1-adrenergic receptor antagonist, α2-adrenergic receptor agonist, and 5-HT1A receptor agonist.[1] Urapidil is currently not approved by the U.S. Food and Drug Administration, but it is available in Europe.

[jim_morrison]

Buspar seems pretty useless, if you really want to blast your 5HT1A receptor, it would make more sence to take an SRI + mirtazapine to block the other 5HT receptors to redirect and simultaneously release more SERT at 5HT1A.

[crayzyMed]

A combo with pindolol would be interesting..

Selective activation of postsynaptic 5-HT1A
receptors induces rapid antidepressant response
by
Blier P; Bergeron R; de Montigny C
Neurobiological Psychiatry Unit,
McGill University, MontrÆeal, Canada.
Neuropsychopharmacology, 1997 May, 16:5, 333-8

ABSTRACT

It has been reported that the 5-HT1A autoreceptor antagonist pindolol can accelerate the antidepressant response to the selective serotonin (5-HT) reuptake inhibitor (SSRI) paroxetine, presumably by preventing the initial decrease in firing activity of 5-HT neurons produced by the SSRI. The present study was aimed at further exploring this treatment strategy in three groups of 10 patients with unipolar major depression allocated sequentially to three treatment arms for 28 days. The administration of the selective 5-HT1A agonist buspirone (20 mg/day for 1 week and 30 mg/day thereafter) with pindolol (2.5 mg TID) was used to activate selectively postsynaptic 5-HT1A receptors. This combination produced a greater than 50% reduction of depressive symptoms in the first week in 8 of 10 patients and the response was sustained for the remainder of the trial. In contrast, the combination of tricyclic antidepressant drugs devoid of effect on the 5-HT reuptake process (desipramine or trimipramine, 75 mg/day for 1 week and 150 mg/day thereafter) with pindolol resulted in only one of ten patients achieving a 50% improvement after 28 days. The combination of the SSRI fluvoxamine (50 mg/day for 1 week and 100 mg/day thereafter) with pindolol produced a marked antidepressant effect but did not act as rapidly as the buspirone plus pindolol combination with none, four, and eight patients achieving a 50% amelioration after 7, 14, and 21 days of treatment, respectively. These results provide further evidence that pindolol may accelerate the antidepressant effect of drugs that alter the function of the 5-HT neurons and that the selective activation of postsynaptic 5-HT1A receptors may induce a rapid and robust antidepressant response.

Apperantly buspar is flawed because it also activates the 5HT1A autoreceptors wich has an opposite effect then the normal 5HT1A receptors.

An effexor, remeron, agomelatine, buspar, pindolol combo should be very effective, maybe a few treatment resistans could try it...
Serotonin rocketfuel 10000++
I would watch out for serotonin syndrome tough.

[crayzyMed]

Originally Posted by euphoria

The brain is a very complicated thing, I don't think it could be reduced to that level of simplicity. Imagine (theoretically) something called "neurotransmitter X", it may affect multiple types of receptors in varying locations of the brain, some could increase "neurotransmitter Y" levels, some could decrease them.

The 5-HT1A receptor is a serotonin (5-HT) receptor, and to answer your question, "5-HT1A receptor activation has been shown to increase dopamine release in the medial prefrontal cortex, striatum, and hippocampus" (just from Wikipedia, I know not a source but w/e).

BTW, I was talking about the 5-HT1A agonists listed on here:

http://www.neurotransmitter.net/newdrugs.html

In Japan they already have one in use AFAIK, called tandospirone.

So yeah, I think serotonin receptors are a hugely important target if you have a mood disorder, even if current methods of doing so are still relatively unsophisticated & clumsy.

If i could tell it would cure me i would fly to japan to get tandospirone lol