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The development of psychotic symptoms is traditionally linked to the increase of the functional activity of endogenous dopaminergic system. Antipsychotic effect of existing medications is associated with direct blockade of postsynaptic dopamine receptors. However, direct antagonistic activity is «alien» to physiological mechanisms of neurotransmission modulation, and presynaptic autoreceptor blockade mау produce a reverse (agonistic) effect, enhancing neurotransmitter release. On the other hand, anti-dopamine effect can be achieved by indirect antagonistic activity—by presynaptic dopamine depletion, which is consistent with the natural, physiological mechanisms of reducing neurotransmission. It can be assumed that modulation of presynaptic regulation is one of the promising directions for the development of antipsychotic drugs of future generations.

The role of agonistic/antagonistic activity in the development of psychotropic effects of antipsychotics