Using amisulpride to block dopamine autoreceptors

Discussion in 'Pharmacology' started by lulz, May 13, 2007.

  1. lulz

    lulz Gold Member

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    I've been interested in this idea for quite some time, has anybody had experience with it?

    To understand the point here, you have to understand how neurons communicate. One neuron fires transmitters towards the next transmitter in the circuit, and if enough of those transmitters attach onto receptors on the next neuron, that neuron activates and fires transmitters towards the folllowing neuron in the chain.

    But on the side of each neuron that is firing the transmitter towards the next one, you find a special type of receptor. Obviously these receptors aren't being targeted by some previous neuron, because they are on the side of the neuron that launches transmitters towards the next neuron in the chain.

    Rather, these receptors act like a thermostat. They are placed on the "firing end" of the neuron to detect when that transmitter has been fired a great deal. When enough of the transmitter has been fired, it will activate these receptors in enough numbers to shut that neuron down.

    These receptors are called "autoreceptors", and they do the exact opposite of normal receptors - instead of activating the neuron, the turn it off.

    Now, the point!

    Typical antipsychotic medications work by blocking dopamine receptors, based on the principle that excessive dopamine transmission is the cause of psychosis.

    But one of these antipsychotics, amisulpride, has an unusual property: in very low doses it antagonises dopamine autoreceptors. That is to say, it attaches to the autoreceptors without activating them.

    By very low doses, I recall reading that this effect is created in the region of 50mg, whereas the therapeautic dose for psychosis is 500mg +

    Unfortunately it seems that google has changed its search algorithms, or research papers have been retired, because I find it hard to locate the research that suggested these findings. Here are a few indications though:

    http://www.ncbi.nlm.nih.gov/entrez/...t_uids=9160856&query_hl=1&itool=pubmed_docsum


    http://www.jimronline.net/content/full/2001/27/0206.pdf


    In theory this could be a great benefit to users of dopamine intensive drugs, amphetamines in particular.

    Has anyone experimented with amisulpride yet?

    I will get around to it sooner or later, but positive results by others would spur him on sooner rather than later.
     
    Last edited: May 13, 2007
  2. stoneinfocus

    stoneinfocus Silver Member

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    Unforunately in the geozaene of swims memories, he thought the onyl arsenal of psychiatry was benzos and happy-pills, and after no-one bought into his really existing depression, he made-up some weird, psychotic symptoms, he read about in the Brockhaus, at a psychiatrist, to get these drugs, ( which he thought would be either benzos or anti-depressives *gg*), but with the psychotic symptoms of paranoia and delusions he made up, he´s gotten away with some sulpiride, which, -big surprise-, he didn´t like at all and threw it a away after a few years of it, lying around, thinking of any benefit, which again is a few years ago.

    Damn good article, by the way! Learned something new at the drive-by, thanks!
     
  3. ladenburg

    ladenburg Silver Member

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    Not amisulpride, but sulpiride. See my post to the anti-psychotics forum:
    https://drugs-forum.com/threads/3796

    The main difference between sulpiride and amisulpride is that the latter is usually taken once daily, while the former is taken 2-3 times a day. In other words, sulpiride 3x50 mg might correspond to amisulpride 1x50 mg.

    For the purposes under discussion here, 50-100 mg per dose would be appropriate.

    Actually, I suspect it would be useless with amphetamines, which already force massive amounts of neurotransmitter into the synapse by emptying storage vesicles into the cytoplasm and reversing the direction of the DAT (dopamine transporter protein). The depletion of dopamine storage vesicles is likely to account for much of the rapid development of tolerance excessive doses of amphetamines - a problem that might even be exacerbated by the addition of autoreceptor antagonists (amisulpride/sulpiride).

    However, there is evidence that sulpiride (and by extension, amisulpride) can potentiate the effects of cocaine (and by extension, methylphenidate, and other DAT inhibitors) - at least in rats. I suspect that the effects can be further intensified by augmentation with L-DOPA or even tyrosine. I would be very interested in reports from such experiments on humans.