Using amisulpride to block dopamine autoreceptors

[lulz]

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:

Both the cueing and the response rate-decreasing effects of apomorphine and 7-OH-DPAT were antagonised by the autoreceptor selective dopamine antagonist amisulpride, and sulpiride also antagonised the cues but without affecting response rates.

http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum

The clinical efficacy of amisulpride against acute psychotic symptoms at high doses, and predominant negative symptoms at low doses, may be explained by its preferential affinity for pre-synaptic dopamine D2 and D3 autoreceptor subtypes at low doses, while higher doses result in antagonism of post-synaptic dopamine receptors.

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?

SWIM will get around to it sooner or later, but positive results by others would spur him on sooner rather than later.