As an adaptive change to blockade of presynaptic D2 receptors (“autoreceptors”) the firing of DA neurons and DA turnover increases initially. However, over a period of time this subsides and gives way to diminished activity, especially in the basal ganglia – corresponds to emergence of parkinsonian effect. Whereas catalepsy arises primarily from acute blockade of postsynaptic D2 receptors. Tolerance to DA turnover enhancing effect of antipsychotics is not prominent in the limbic area – may account for the continued antipsychotic effect (fig. 9,10).

Fig. 9. Sites of action of many antipsychotic drugs on DA neurotransmission.

Blockade of presinaptic receptors increases DA synthesis (1) and release (2) and can reduce passage of K+ though an anion channel. Classic antipsychotic drugs also block postsynaptic DA receptors (3). D2 -DA receptor; G – guanine nucleotide binding protein (G-protein). G-GDP and G-GTP represent G protein bound to either guanosine diphosphate of guanosine triphosphate, respectively.