Posted by JohnX on February 15, 2001, at 9:14:37
In reply to my Amisulpride efficacy hypothesis, posted by bornunderabadsign on February 12, 2001, at 4:33:41
>
>
> I considered this over my Cap'n Crunch this morning:
> Given the two states of dopamine transmission: Basal and Pulsatile, how does amisulpride effect such transmission. When should it work and when should it not work.
>
>
> I tried amisulpride 10mg/day for a month, and noticed no subjective mitigation of symptoms.
>
> I have just started wellbutrin sr 150mg/day. My idea is this:
>
> Pulsatile, or hyperpolarization-modulated DA exocytosis is believed to be regulated by presynaptic Auto-Receptors, which Amisulpride is believed to act upon.
>
> My hypothesis is this: Basal, or "backround" levels of DA are regulated by the amount of DA transport in the synapse. Therefore, such an inverse relationship can be stated:
>
> 1
> _______________________ = level of DA transport
>
> Efficacy of Amisulpride
>
> Moreover, it is possible that Wellbutrin modulates basal level of DA, and, therefore the workings of DA transport.
>
> Indeed, Wellbutrin is anything but immutable, sometimes making things worse, and sometimes better. Wellbutrin blocks Dopamine (DA) *reuptake*, while, at the same time *decreasing* release.
>
> Obviously, I have conducted no formal trial of such a hypothesis, however, these phenomenon may support it:
>
> 1.) Greater success of Amisulpride in Wellbutrin-resistant patients.
>
> 2.) Less success of Amisulpride in those who recently built a tolerance to psycho-stimulants.
>
> 3.) Less signficant success, or failure, of amisulpride in Wellbutrin-successful patients.
>
> Not sure, but any comments would be welcome. I should know in a few weeks if the wellbutrin works for me where Adderall has gradually failed.
>
> Elvis has left the building,
>
> -JamesJames/Andrew,
I prefer Lucky Charms , but anyways....
Heres my *long* analysis to date, I'm currently
trying to look into fields that Andrew is more
familiar with to also understand Amisulpride and
my other data points. I'm no expert, I design chips
not brains, but I prefer to use deductive logic
to tailor my medication instead of throwing darts.I have been trying to correlate my responses to
Wellbutrin, Zoloft, Adderall (stand-alone), Adderall + Klonopin.
Later, I'll have some Amisulpride data.I have been trying to understand the mechanism of action of Wellbutrin
since it was one of the anti-depressants that I got a response from.
The other was Zoloft. I tend to be very sensitive to chemicals.
Sometimes I can induce a manic state, but it always is preceded
by chemical injestion. I think this "technically" rules me out as bipolar,
but whatever.Anyways, when I get a response, usually I have a short lived (hypo)manic episode
followed by an irratic transition to a state of complete emotional numbing with
massive muscle contraction facial pain. I talked about this with Andrew, and I
kinda described it as a ping pong from positive psychosis to negative psychosis.
The muscle contraction and loss of emotion is likely an indicator of a
hypo-dopaminergic prefrontal cortex (this is where the neurons for the facial muscles are).Zoloft:
Zoloft would knock out my emotions and cause facial pain after ~3 days
pre anti-depressant response and then after about 7 days, the anti-depressant would
kick for a short while, my emotions would return and the pain goes away, and then
I would switch back to the bizarre loss of affect and facial pain. I read a paper
regarding Zoloft's tendency to induce contraction headaches.
The hypothesis was that sorotonin neurons innervating the VTA modulate
the firing rate of the VTA dopamine neurons into the mPFC.
Purportedly, 5ht-1 inputs increase the firing and 5ht-2 slow the firing.
So, the paper suspected that Zoloft banging on 5ht-2 (until down-regulation?)
decreased the firing rate of the VTA dopamine neurons causing the problem.
I read another abstract stating that SSRIs can slightly reduce the
basal firing of VTA neurons. I guess if you are more sensitive, then
it can *greatly* reduce the firing rate?Adderall:
I also have been trying to understand why I get quick poop-out (~3 days)
when I take Aderrall stand-alone. When Aderall works, it
alleviates my facial pain, but this could be unrelated to the VTA since
it will increase dopamine elsewhere. I just read the latest and greatest
paper which shows that amphetamine sensitization starts with amphetamine
induced *serotonin* release in the VTA (A10), which in turn *decreases*
NMDA glutamate release and long-term (short term for me) triggers a down stream
sensitization. I found another abstract that claims 5ht2 antagonists reverse
amphetamine induced slowing of A10 dopamine neuronal firing. How do the
5ht-2 receptors control serotonin release? If they are down-regulated
by an anti-depressant, would this reduce serotonin release and evoke
more burst like firing in the VTA ? The amphetamine paper also punched the dopamine
receptors D1 and D2 with agonists/antagonists. It found that they could
not suppress the amphetamine reduction of glutamate transmission. However
Sulpride, a D2 antagonis,did reduce net amphetamine evoked dopamine
transmission. Any thoughts? We suspect NMDA-partial agonists
would prevent sensitization (so does Klonopin, I'm trying to find out why).Wellbutrin:
Anyways, I read another paper on Wellbutrin which tries to theorize its
mode of action and who would be non responders. Here is my Wellbutrin
response: until the anti-depressant kicks in, it doesnt affect me at all,
when it kicks in , it pulls a Zoloft. The difference is that it doesn't zap
my emotions pre-response. The paper indicates that Wellbutrin reduces
whole body norepinephrine turnover (explain please?). Responders showed
no changes in plasma HVA (explain please?). Non-responders sowed a small
increase. It also hypothesized that the metabolite hydroxy-buproprion was
paying most of the bill via blockade of norepinephrine reuptake & decreased
tyrosine hydroxylase immunoreactivity.
Thus this would reduce monoamine production in some areas of the brain
both for dopamine and norepinephrine but increase re-uptake.
Perhaps this explains why it can reduce release of dopamine,
and sensitize the dopamine neurons (who wins?).
At dosed needed for an anti-depressant response, raphe serotonergic
firing rates are not affected, nor are firing rates of A9,A10 neurons.
At toxic doses, the firing rate of A10 neurons is slowed to a crawl
(doesn't explain why). I suspect in my case that I am not hitting
toxic doses, but some feedback after the response causes a substantial
reduction in A10 firing - thus the numbing and facial pain.Any thoughts?
What would Amisulpride do?-John
poster:JohnX
thread:53790
URL: http://www.dr-bob.org/babble/20010212/msgs/54053.html