"Hit-and-Run" actions at dopamine receptors, part 2: Illustrating fast dissociation from dopamine receptors that typifies atypical antipsychotics.

Postsynaptic Neuron Figure 1. Conventional vs. Atypical Antipsychotic Mechanisms n last month’s BRAINSTORMS, we discussed a new hypothesis on the mechanism of action of atypical antipsychotics, namely the “hit-and-run” hypothesis. Here we illustrate this concept. Conventional: Because of the biochemical properties of conventional antipsychotics, their binding to postsynaptic dopamine D2 receptors is tight and long lasting, as shown by the teeth on the binding site of the conventional antipsychotic (A). The D2 receptor on the right has grooves where the teeth of the drug can bind tightly, locking the drug into the receptor binding site (B) to block it in a long-lasting manner.