@Hip is the first person I know who started experimenting with antipsyhcotics and he mentioned clearly that lower dose is the effective dose (works differently on lower dose).
Yes, for these third generation antipsychotics like amisulpride and aripiprazole, these drugs are classed as
dopamine system stabilizers, which means the drug acts as an agonist of the dopamine receptors at low dopamine concentrations, but acts as an antagonist at high dopamine concentrations.
So these drugs boost the dopamine system when dopamine is low, but put the breaks on the dopamine system when dopamine is high. Refs:
1 2
The response to amisulpride is also dose-level dependent:
At
low doses, amisulpride blocks the dopamine autoreceptors. An autoreceptor is presynaptic regulatory feedback mechanism which controls how much of a neurotransmitter like dopamine is being released into the synapse (the junction between neurons). When you block the dopamine autoreceptors, it makes the neuron think there is not enough dopamine in the synapse, so more dopamine is released. In this way, blocking dopamine autoreceptors leads to more dopamine release.
But at
high doses of amisulpride, then this drug starts to antagonize the postsynaptic dopamine receptor (the normal dopamine receptor), and at these higher doses the overall effect is dopamine antagonism. Refs:
1 2
Aripiprazole behaves similarly at the presynaptic and postsynaptic dopamine receptors.
This paper says:
There is evidence that aripiprazole functions as both a presynaptic D2 agonist and post synaptic D2 antagonist. Presynaptic D2 autoreceptors may play a vital role in the ability of aripiprazole to act as a DA system stabilizer, but at higher doses (such as the ones used to treat schizophrenia), aripiprazole also has a significant binding affinity at post synaptic D2 receptors.
Some more info in the first post of
this thread.
