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.
poster:iforgotmypassword
thread:929841
URL: http://www.dr-bob.org/babble/20091217/msgs/929960.html