Dopamine System Stabilizers, Aripiprazole, and the Next Generation of Antipsychotics, Part 1: "Goldilocks" Actions at Dopamine Receptors

Psychosis occurs when too much dopamine exists in the synapses, and the action, akin to Goldilocks’s first bowl of soup, is "too hot." Every antipsychotic that reduces the positive symptoms of psychosis such as delusions and hallucinations does so by blocking dopamine D2 receptors, most likely those of the mesolimbic dopamine pathway. Unfortunately, the blocking is often nonspecific, which is typical of conventional antipsychotic actions. Thus, when D2 receptors in the nigrostriatal dopamine pathway are also blocked, a penalty is paid in motor side effects, namely extrapyramidal reactions, pseudoparkinsonism, and ultimately, tardive dyskinesia.