Posted by SLS on June 14, 2000, at 8:56:47
In reply to Re: Incomplete recovery - SLS, posted by KarenB on June 13, 2000, at 11:54:05
Dear Karen,
Hi.
> > Perhaps low serotonin is never the cause.> You may be right...
> > Perhaps dopaminergic drugs make a good bandage to compensate for the underactivity of GLUTAMATERGIC neurons afferent to the thalamus and hippocampus that have been downregulated due to their chronic overactivity in response to stress. This would allow for a perturbation of the balance between GLUTAMATERGIC and GABAergic activity there in favor of efferent GABAergic neurons leading to the nucleus accumbens, whereby dopaminergic neurotransmission in this healthy structure is thus inhibited. What do you think?
> I think I want a new brain.
Take a number.
> By the way, you may remember that Amineptine combined with Sulpiride worked best for me. I'm trying to find alternatives here, stateside. Right now, it's Adderall and Buspar - OK but not totally there yet. I'm going to trial Modafinil starting next week - I have faxed info to doc (he knoweth not the med) and if he won't let me trial it, I go elsewhere. Adderall has me clenching my jaws by afternoon - but, at least I have energy. Like I said, OK but not great...
Again, I consider the combination of sulpiride/amisulpride with amineptine to be one of the most well conceived strategies I have come across. As far as what to use as a replacement for amineptine, I have given it some thought, but haven't come up with much. I have mentioned to a few doctors a drug called mazindol (Mazinor, Sanorex) as a candidate to fill this role. to a few doctors, but it I did not receive any feedback. I doubt it has been considered as a potential augmenting agent, at least not in the last 15 years. Like amineptine, it is a reuptake inhibitor of both dopamine and norepinephrine without promoting the release of either.
I am beginning to wonder if combining Serzone with a dopaminergic drug may be particularly effective. I may consider trying it before heading back to Parnate. Have you ever tried Serzone alone or in combination with anything? It might go well with sulpiride - sort of like a more selective Zyprexa. Anyway, it looks good to me on paper (or a webpage).
Modafinil (Provigil) or Adrafinil (Olmifon) look to be interesting drugs that might provide utility as adjunctive or augmenting drugs. As can be seen from JohnL's experience it seems to go quite well with amisulpride.
This evening, I hope to be able to send a FAX to London and place an order for sulpiride. My doctor consulted with a colleague in NYC who has had a great deal of experience with sulpiride. It is his opinion that sulpiride is superior to amisulpride for treating depression. I'm not happy to hear about the weigh-gain thing, but 10 pounds is not an unreasonable price to pay for my resurrection. Interestingly, this doctor stated that one either responds early or doesn't respond at all. From what I can see here, that seems to hold true, as some people experience little more than profound sedation with no antidepressant response to be later obtained.
>
> In your opinion, does the Amineptine/Sulpiride success indicate dopamine depletion?It sure sounds like a logical possibility. It may be that there is a reduced rate of synthesis of dopamine within the presynaptic neuron. The gas tank is always near empty. Sulpiride and amisulpride tell the neuron to assemble more dopamine molecules. It also tells it to release more of them when it is asked to. MAO inhibitors tell the neuron not to waste any dopamine molecules by preventing it from disassembling them. Amineptine tells the neuron to leave the released molecules outside and not let them back in. This allows the released dopamine to accumulate near the postsynaptic neuron and stimulates it to fire, sending the message on the the next one.
> What up with the glutaminergic thing?
I'm not sure. I was just guessing about the stress thing.
I'm sorry that I misspelled the word. It should be "glutamatergic" derived from the name of the excitatory neurotransmitter, glutamate.
Scientists seem pretty confident that Provigil causes the levels of glutamate outside the cell to increase, possibly by promoting its release. This seems to turn-off the GABA neurons. GABA neurons tell dopamine neurons to "shut-up". Now these dopaminergic neurons are allowed to talk more.
Provigil => More glutamate => Less GABA => More talkative dopamine neurons.
It is unclear whether or not Provigil affects norepinephrine directly.
Lamictal may do just the opposite. It may decrease the release of glutamate, allowing GABA neurons to tell overly-talkative dopamine neurons to quiet down. Perhaps this is why Lamictal can quiet overly-talkative people who are in a manic state.
Lamictal => Less glutamate => More GABA => Less talkative dopamine neurons. (possibly)
Some of the other anticonvulsant mood stabilizers also seem to increase GABA activity, although through other mechanisms.
GABA is a neurotransmitter that generally helps to prevent areas of the brain from getting overly excited. It helps quiet many different types of neurons in addition to dopaminergic ones.
> Is it possible that GABA supplementation could help in a case like this or am I way off base?
I didn't know there were GABA supplements. I don't know enough about it to comment.
Good thinking, though.
> Hope you are doing well.
I'm not, but thank you so much for asking.
- Scott
poster:SLS
thread:36813
URL: http://www.dr-bob.org/babble/20000610/msgs/37254.html