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Dr. Bob is Robert Hsiung, MD,
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Posted by B2chica on November 14, 2007, at 8:59:59
Sigma-1 receptor
for those that don't want to read the whole thing.
my question is, how is the sigma-1 receptor different from the DA receptors...is it dopamine effecting?
do the same meds that are used for DA receptors used with the sigma receptor? and is there much research on it?
and i would like to learn more about experiences of psychotic depression...any websites..or personal experiences i'd like to know..
thanks.NOW for the Long version:
i've been doing some reading about the 5-ht2 receptor and DA receptors.
several years ago i was Dx with Bipolar2...i new i've always had depression but i had a friend that was truly Bipolar and just never quite felt like i fit....the 'episodes' that i would describe to my (prev) docs would say i was manic...a dysphoric mania...maybe so. ..but the more i've been reading lately, i feel that i fit better in the descriptors of psychotic depression.
i hadn't even heard of this descriptor before.
here is what they generally list:
-anxiety
-agitation
-aggression
-hypochondria
-insomnia
-physical immobility
-constipation
-cognitive impairment
-psychosisi've suffered from 8 of those.
the docs kept asking (re: mania) do you ever feel REALLY good....well, i have but i always tell them i will be severly depressed then i feel really good for about 2 days and then it turns "dysphoric" using their terms. it could get pretty severe....extreme rage, soon turning inward, i'd hear this kinda voice in my head telling me nasty things and sometimes acting on them....i several times spun into a severe psychotic episode (delusional thinking...not like i think famous actor loves me or something but i believe people can hear my thoughts, or my inner voice warns me of things/people...etc.)....the docs kept telling me its mania..i later switched to a differend pdoc (i really liked him), he was never convinced that i was bipolar but never told me anything else.
lately during therapy and stopping breastfeeding my depression has come back with a vengance.
this time im keeping track of all my "oddities". and it seems that when i see my shadow things and hear things it's during the lowest of my depressive phase, EVEN though i feel Energized....it's not a good energy. it makes me shaky and scared and angry and i just want to "hurt myself very badly" to remain civil.
quite frankly i get "wacked out". but it happens During my depressive phase.back to above questions.
thank you for listening
b2c
Posted by Phillipa on November 14, 2007, at 11:49:22
In reply to Sigma-1 receptor/Psychotic Depression Ques..., posted by B2chica on November 14, 2007, at 8:59:59
You say this is coming back after breast feeding could prolactin be involved? What meds are you currently on? I fit the description of anxiety, was not sleeping now that all I want to do. What meds do you think would help you? Is does seem like there is some psychosis there any antipsychotics? I wish I knew more. Phillipa
Posted by Astounder on November 15, 2007, at 19:52:17
In reply to Sigma-1 receptor/Psychotic Depression Ques..., posted by B2chica on November 14, 2007, at 8:59:59
> Sigma-1 receptor
>
> for those that don't want to read the whole thing.
> my question is, how is the sigma-1 receptor different from the DA receptors...is it dopamine effecting?
> do the same meds that are used for DA receptors used with the sigma receptor? and is there much research on it?
> and i would like to learn more about experiences of psychotic depression...any websites..or personal experiences i'd like to know..
> thanks.
Sigma receptors are very, very poorly characterized. We know at least they have something to do with plastic changes in DA neurons, and play a role in drug sensitization. Lots are things are ligands for them: Ketamine, DXM, PCP, kappa-opioidergic analgesics, psychostimulants, some SSRIs, Haldol, various hormones--and of these we really don't know which are agonists and which are antagonists. They were being examined back when dissociatives started to be viewed as a superior drug model of schizophrenia and we didn't really understand their binding well: Two sites were known, the sigma "opioid" receptor, and the PCP-binding site.It's now known that the PCP-binding site is inside the pore of the NMDA channel complex, where ligands act as pure channel blockers (uncompetitive antagonists), and this is the mechanism of action of the dissociatives, including their psychotomimetic effect. The sigma receptor does not seem to mediate the acute actions of the dissociatives, and selective sigma ligands have not shown efficacy as antipsychotics in animal models.
I was originally looking at them at one time as a drug model of depersonalization, but I ended up disappointed.
If you're looking for a novel treatment for psychotic depression, you should look into D-serine, which is a functional agonist of the NMDA receptor PCP binds to. There have been humans studies indicating utility in schizophrenia.
Posted by linkadge on November 15, 2007, at 22:17:29
In reply to Re: Sigma-1 receptor/Psychotic Depression Ques... » B2chica, posted by Astounder on November 15, 2007, at 19:52:17
Fluvoxamine has shown stronger effiacy in psychotic depression than other SSRI agents. I think there was the presumption that its binding for sigma receptors had something to do with this.
Sigma receptors inteact with nerve growth factor to produce certain trophic actions in neurons. Sigma receptors appear to be capable of mediating antidepressant effects on their own.
The mood elevating effects of DHEA might be a mediated by sigma receptors as DHEA binds to sig-1r. But then again, DHEA is no antipsyhotic!
Many of the typtical antipsychotics are antagonists at sigma receptors, so this confuses the model as fluvoxamine is an agonist.
Sigma 1r receptor agonism appears to have some nootropic activity, which may mediate the effectiveness of fluvoxamine in psychotic depression. I read destinct theory that regarding the activity of sig-1r receptors on brain lipid metabolsm which may be of relavance to mood disorders.
Linkadge
Posted by Phillipa on November 16, 2007, at 18:05:05
In reply to Re: Sigma-1 receptor/Psychotic Depression Ques..., posted by linkadge on November 15, 2007, at 22:17:29
Link so are you saying that fluvoximine is good for psychotic depression? Phillipa
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